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Methylglyoxal from gut microbes boosts radiosensitivity and radioimmunotherapy in rectal cancer by triggering endoplasmic reticulum stress and cGAS-STING activation. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-30 Han Zhou,Lei Wang,Zhiwen Lin,Chenwei Jiang,Xingte Chen,Kai Wang,Libin Liu,Lingdong Shao,Jianji Pan,Jinluan Li,Da Zhang,Junxin Wu
BACKGROUND Preoperative radiation therapy (preRT) is a fundamental aspect of neoadjuvant treatment for rectal cancer (RC), but the response to this treatment remains unsatisfactory. The combination of radiation therapy (RT) and immunotherapy (iRT) presents a promising approach to cancer treatment, though the underlying mechanisms are not yet fully understood. The gut microbiota may influence the response
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Evaluation of tissue- and plasma-derived tumor mutational burden (TMB) and genomic alterations of interest in CheckMate 848, a study of nivolumab combined with ipilimumab and nivolumab alone in patients with advanced or metastatic solid tumors with high TMB. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-30 Jie He,Natallia Kalinava,Parul Doshi,Dean C Pavlick,Lee A Albacker,Ericka M Ebot,Hanna Tukachinsky,James Pratt,Gina Fusaro,Geoffrey R Oxnard,George Green,David Fabrizio,Jonathan Baden
BACKGROUND An accumulation of somatic mutations in tumors leads to increased neoantigen levels and antitumor immune response. Tumor mutational burden (TMB) reflects the rate of somatic mutations in the tumor genome, as determined from tumor tissue (tTMB) or blood (bTMB). While high tTMB is a biomarker of immune checkpoint inhibitor (ICI) treatment efficacy, few studies have explored the clinical utility
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Phase I/Ib, open-label, multicenter, dose-escalation study of the anti-TGF-β monoclonal antibody, NIS793, in combination with spartalizumab in adult patients with advanced tumors. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-29 Todd M Bauer,Armando Santoro,Chia-Chi Lin,Ignacio Garrido-Laguna,Markus Joerger,Richard Greil,Anna Spreafico,Thomas Yau,Maria-Elisabeth Goebeler,Marie Luise Hütter-Krönke,Antonella Perotti,Pierre-Eric Juif,Darlene Lu,Louise Barys,Viviana Cremasco,Marc Pelletier,Helen Evans,Claire Fabre,Toshikiko Doi
BACKGROUND NIS793 is a human IgG2 monoclonal antibody that binds to transforming growth factor beta (TGF-β). This first-in-human study investigated NIS793 plus spartalizumab treatment in patients with advanced solid tumors. METHODS Patients received NIS793 (0.3-1 mg/kg every 3 weeks (Q3W)) monotherapy; following evaluation of two dose levels, dose escalation continued with NIS793 plus spartalizumab
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Delayed vaccine-induced CD8+ T cell expansion by topoisomerase I inhibition mediates enhanced CD70-dependent tumor eradication. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-29 Tetje C van der Sluis,Floortje J van Haften,Suzanne van Duikeren,Iris N Pardieck,J Fréderique de Graaf,Ward Vleeshouwers,Koen van der Maaden,Cornelis J M Melief,Sjoerd H van der Burg,Ramon Arens
BACKGROUND The survival of patients with cervical cancer who are treated with cisplatin in conjunction with the topoisomerase I inhibitor topotecan is enhanced when compared with patients treated with only one of these chemotherapeutics. Moreover, cisplatin-based and T cell-based immunotherapy have been shown to synergize, resulting in stronger antitumor responses. Here, we interrogated whether topotecan
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TP53/mTORC1-mediated bidirectional regulation of PD-L1 modulates immune evasion in hepatocellular carcinoma. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-29 Jiongjie Yu,Sunbin Ling,Jiachen Hong,Lincheng Zhang,Wei Zhou,Lu Yin,Shengjun Xu,Qingyang Que,Yongfeng Wu,Qifan Zhan,Jiaqi Bao,Nan Xu,Yuchen Liu,Kangchen Chen,Xuyong Wei,Zhikun Liu,Tingting Feng,Lin Zhou,Haiyang Xie,Shuai Wang,Jimin Liu,Shusen Zheng,Xiao Xu
BACKGROUND Immunotherapy has facilitated great breakthroughs in the treatment of hepatocellular carcinoma (HCC). However, the efficacy and response rate of immunotherapy are limited and vary among different patients with HCC. TP53 mutation substantially affects the expression of immune checkpoint molecules in multiple cancers. However, the regulatory relationship between programmed death ligand 1 (PD-L1)
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MDSCs-derived GPR84 induces CD8+ T-cell senescence via p53 activation to suppress the antitumor response. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-28 Jinyan Liu,Jiayin Liu,Guohui Qin,Jiahui Li,Ziyi Fu,Jieyao Li,Miaomiao Li,Caijuan Guo,Ming Zhao,Zhen Zhang,Feng Li,Xuan Zhao,Liping Wang,Yi Zhang
BACKGROUNDS G-protein-coupled receptor 84 (GPR84) marks a subset of myeloid-derived suppressor cells (MDSCs) with stronger immunosuppression in the tumor microenvironment. Yet, how GPR84 endowed the stronger inhibition of MDSCs to CD8+ T cells function is not well established. In this study, we aimed to identify the underlying mechanism behind the immunosuppression of CD8+ T cells by GPR84+ MDSCs.
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High-dimensional single-cell proteomics analysis of esophageal squamous cell carcinoma reveals dynamic alterations of the tumor immune microenvironment after neoadjuvant therapy. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-28 Dingpei Han,Yichao Han,Wei Guo,Wei Wei,Su Yang,Jie Xiang,Jiaming Che,Lianggang Zhu,Junbiao Hang,Tom van den Ende,Hanneke W M van Laarhoven,Bin Li,Youqiong Ye,Hecheng Li
BACKGROUND Dynamic alterations of the tumor immune microenvironment in esophageal squamous cell carcinoma (ESCC) after different neoadjuvant therapies were understudied. METHODS We used mass cytometry with a 42-antibody panel for 6 adjacent normal esophageal mucosa and 26 tumor samples (treatment-naïve, n=12; postneoadjuvant, n=14) from patients with ESCC. Single-cell RNA sequencing of previous studies
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Randomized, open-label, phase II, biomarker study of immune-mediated mechanism of action of neoadjuvant subcutaneous trastuzumab in patients with locally advanced, inflammatory, or early HER2-positive breast cancer-Immun-HER trial (GOIRC-01-2016). J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-28 Benedetta Pellegrino,Chiara Tommasi,Olga Serra,Stefania Gori,Elisabetta Cretella,Massimo Ambroggi,Antonio Frassoldati,Giancarlo Bisagni,Chiara Casarini,Emilio Bria,Luisa Carbognin,Elena Fiorio,Antonella Mura,Claudio Zamagni,Lorenzo Gianni,Alberto Zambelli,Filippo Montemurro,Michele Tognetto,Renata Todeschini,Gabriele Missale,Nicoletta Campanini,Enrico Maria Silini,Giuseppe Maglietta,Antonino Musolino
BACKGROUND It is possible to induce immunomodulation in HER2-positive breast cancer (BC) by modifying the route of administration of trastuzumab. METHODS In this multicenter randomized phase II trial, all enrolled patients (pts) with T2-T4d HER2-positive BC received 3 cycles of neoadjuvant treatment (NAT) with fluorouracil, epirubicin and cyclophosphamide every 3 weeks (q21), followed by docetaxel/pertuzumab
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Assessment and predictive ability of the absolute neutrophil count in peripheral blood for in vivo CAR T cells expansion and CRS. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-27 Man Zhang,Xiaolu Long,Yi Xiao,Jin Jin,Caixia Chen,Jiao Meng,Wanying Liu,Aichun Liu,Liting Chen
BACKGROUND Chimeric antigen receptor (CAR) T cell therapy is an advanced and effective immunotherapy for relapsed or refractory B-cell malignancies. High expansion of CAR T cells in vivo and durable antitumor activity indicate a persistent therapeutic response. However, this treatment is linked to a high frequency of adverse events, such as cytokine release syndrome (CRS), which affects its efficacy
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Guidelines for immunological analyses following focused ultrasound treatment. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-24 Frederic Padilla,Jessica Foley,Kelsie Timbie,Timothy N J Bullock,Natasha D Sheybani
Focused ultrasound (FUS) is a powerful emerging tool for non-invasive, non-ionizing targeted destruction of tumors. The last two decades have seen a growing body of preclinical and clinical literature supporting the capacity of FUS to increase nascent immune responses to tumors and to potentiate cancer immunotherapies (e.g. checkpoint inhibitors) through a variety of means, including immune modulation
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CDK5 destabilizes PD-L1 via chaperon-mediated autophagy to control cancer immune surveillance in hepatocellular carcinoma. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-24 Ruonan Zhang,Jie Wang,Yu Du,Ze Yu,Yihan Wang,Yixiao Jiang,Yixin Wu,Ting Le,Ziqi Li,Guoqiang Zhang,Lei Lv,Haijie Ma
BACKGROUND In the past few years, immunotherapies of hepatocellular carcinoma (HCC) targeting programmed cell death protein 1 (PD-1) and its ligand programmed cell death ligand 1 (PD-L1), have achieved durable clinical benefits. However, only a fraction of HCC patients showed objective clinical response to PD-1/PD-L1 blockade alone. Despite the impact on post-translational modifications of PD-L1 being
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Therapeutic avenues for γδ T cells in cancer. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-24 Gonçalo Palrão Costa,Sofia Mensurado,Bruno Silva-Santos
γδ T cells are regarded as promising effector lymphocytes for next-generation cancer immunotherapies. In spite of being relatively rare in human peripheral blood, γδ T cells are more abundant in epithelial tissues where many tumors develop, and have been shown to actively participate in anticancer immunity as cytotoxic cells or as "type 1" immune orchestrators. A major asset of γδ T cells for tackling
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Single-cell RNA-sequencing atlas reveals an FABP1-dependent immunosuppressive environment in hepatocellular carcinoma. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-24 Weiwei Tang,Guangshun Sun,Gu-Wei Ji,Tingting Feng,Qian Zhang,Hengsong Cao,Wenhao Wu,Xiaoyi Zhang,Chuan Liu,Hanyuan Liu,Tian Huang,Li Liu,Yongxiang Xia,Xuehao Wang
BACKGROUND Single-cell RNA sequencing, also known as scRNA-seq, is a method profiling cell populations on an individual cell basis. It is particularly useful for more deeply understanding cell behavior in a complicated tumor microenvironment. Although several previous studies have examined scRNA-seq for hepatocellular carcinoma (HCC) tissues, no one has tested and analyzed HCC with different stages
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Chimeric antigen receptor T cells to target CD79b in B-cell lymphomas. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-24 Fuliang Chu,Jingjing Cao,Jingwei Liu,Haopeng Yang,Timothy J Davis,Shao-Qing Kuang,Xiaoyun Cheng,Zheng Zhang,Swathi Karri,Long T Vien,Laura Bover,Ryan Sun,Francisco Vega,Michael Green,Richard Eric Davis,Sattva S Neelapu
BACKGROUND Chimeric antigen receptor (CAR) T cells targeting CD19 mediate potent and durable effects in B-cell malignancies. However, antigen loss or downregulation is a frequent cause of resistance. Here, we report development of a novel CAR T-cell therapy product to target CD79b, a pan B-cell antigen, widely expressed in most B-cell lymphomas. METHODS We generated a novel anti-CD79b monoclonal antibody
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Framework humanization optimizes potency of anti-CD72 nanobody CAR-T cells for B-cell malignancies. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-24 William C Temple,Matthew A Nix,Akul Naik,Adila Izgutdina,Benjamin J Huang,Gianina Wicaksono,Paul Phojanakong,Juan Antonio Camara Serrano,Elizabeth P Young,Emilio Ramos,Fernando Salangsang,Veronica Steri,Simayijiang Xirenayi,Michelle Hermiston,Aaron C Logan,Elliot Stieglitz,Arun P Wiita
BACKGROUND Approximately 50% of patients who receive anti-CD19 CAR-T cells relapse, and new immunotherapeutic targets are urgently needed. We recently described CD72 as a promising target in B-cell malignancies and developed nanobody-based CAR-T cells (nanoCARs) against it. This cellular therapy design is understudied compared with scFv-based CAR-T cells, but has recently become of significant interest
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Neuroblastoma: an ongoing cold front for cancer immunotherapy. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-22 Paul T Kennedy,Demetra Zannoupa,Meong Hi Son,Lekh N Dahal,John F Woolley
Neuroblastoma is the most frequent extracranial childhood tumour but effective treatment with current immunotherapies is challenging due to its immunosuppressive microenvironment. Efforts to date have focused on using immunotherapy to increase tumour immunogenicity and enhance anticancer immune responses, including anti-GD2 antibodies; immune checkpoint inhibitors; drugs which enhance macrophage and
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Tumor cell-induced macrophage senescence plays a pivotal role in tumor initiation followed by stable growth in immunocompetent condition. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-01 Haruka Wada,Ryo Otsuka,Wilfred T V Germeraad,Tomoki Murata,Toru Kondo,Ken-Ichiro Seino
BACKGROUND The cancer stem cell theory proposes that tumor formation in vivo is driven only by specific tumor-initiating cells having stemness; however, clinical trials conducted to test drugs that target the tumor stemness provided unsatisfactory results thus far. Recent studies showed clear involvement of immunity in tumors; however, the requirements of tumor-initiation followed by stable growth
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Systemic infusion of TLR3-ligand and IFN-α in patients with breast cancer reprograms local tumor microenvironments for selective CTL influx. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-01 Shipra Gandhi,Mateusz Opyrchal,Melissa J Grimm,Ronald T Slomba,Kathleen M Kokolus,Agnieszka Witkiewicz,Kristopher Attwood,Adrienne Groman,Lauren Williams,Mary Lynne Tarquini,Paul K Wallace,Kah Teong Soh,Hans Minderman,Orla Maguire,Tracey L O'Connor,Amy P Early,Ellis G Levine,Pawel Kalinski
BACKGROUND Presence of cytotoxic T lymphocytes (CTL) in the tumor microenvironment (TME) predicts the effectiveness of cancer immunotherapies. The ability of toll-like receptor 3 (TLR3) ligands, interferons (IFNs) and COX2 inhibitors to synergistically induce CTL-attracting chemokines (but not regulatory T cell (Treg)-attractants) in the TME, but not in healthy tissues, observed in our preclinical
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Targeting the aryl hydrocarbon receptor (AhR) with BAY 2416964: a selective small molecule inhibitor for cancer immunotherapy. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-01 Christina Kober,Julian Roewe,Norbert Schmees,Lars Roese,Ulrike Roehn,Benjamin Bader,Detlef Stoeckigt,Florian Prinz,Mátyás Gorjánácz,Helge Gottfried Roider,Catherine Olesch,Gabriele Leder,Horst Irlbacher,Ralf Lesche,Julien Lefranc,Mine Oezcan-Wahlbrink,Ankita Sati Batra,Nirmeen Elmadany,Rafael Carretero,Katharina Sahm,Iris Oezen,Frederik Cichon,Daniel Baumann,Ahmed Sadik,Christiane A Opitz,Hilmar Weinmann
BACKGROUND The metabolism of tryptophan to kynurenines (KYN) by indoleamine-2,3-dioxygenase or tryptophan-2,3-dioxygenase is a key pathway of constitutive and adaptive tumor immune resistance. The immunosuppressive effects of KYN in the tumor microenvironment are predominantly mediated by the aryl hydrocarbon receptor (AhR), a cytosolic transcription factor that broadly suppresses immune cell function
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Local and distant response to intratumoral immunotherapy assessed by immunoPET in mice. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-01 Louis Meyblum,Céline Chevaleyre,Sandrine Susini,Benoit Jego,Frederic Deschamps,Dimitri Kereselidze,Baptiste Bonnet,Aurelien Marabelle,Thierry de Baere,Vincent Lebon,Lambros Tselikas,Charles Truillet
BACKGROUND Despite the promising efficacy of immune checkpoint blockers (ICB), tumor resistance and immune-related adverse events hinder their success in cancer treatment. To address these challenges, intratumoral delivery of immunotherapies has emerged as a potential solution, aiming to mitigate side effects through reduced systemic exposure while increasing effectiveness by enhancing local bioavailability
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Timed adoptive T cell transfer during chemotherapy in patients with recurrent platinum-sensitive epithelial ovarian cancer. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-01 Els M E Verdegaal,Saskia J Santegoets,Marij J P Welters,Linda de Bruin,Marten Visser,Caroline E van der Minne,Pita M de Kok,Nikki M Loof,Sanne Boekestijn,Inge Roozen,Inge M Westra,Pauline Meij,Sjoerd H Van der Burg,Judith R Kroep
BACKGROUND The presence of T cells and suppressive myeloid cells in epithelial ovarian cancer (EOC) correlate with good and bad clinical outcome, respectively. This suggests that EOC may be sensitive to adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL), provided that immunosuppression by myeloid-derived suppressor cells and M2 macrophages is reduced. Platinum-based chemotherapy
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New perspectives in cancer immunotherapy: targeting IL-6 cytokine family. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-01 Maria Florencia Soler,Andrea Abaurrea,Peio Azcoaga,Angela M Araujo,Maria M Caffarel
Chronic inflammation has been recognized as a canonical cancer hallmark. It is orchestrated by cytokines, which are master regulators of the tumor microenvironment (TME) as they represent the main communication bridge between cancer cells, the tumor stroma, and the immune system. Interleukin (IL)-6 represents a keystone cytokine in the link between inflammation and cancer. Many cytokines from the IL-6
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Unraveling the impact of sialic acids on the immune landscape and immunotherapy efficacy in pancreatic cancer. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-01 Kelly Boelaars,Laura Goossens-Kruijssen,Di Wang,Charlotte M de Winde,Ernesto Rodriguez,Dimitri Lindijer,Babet Springer,Irene van der Haar Àvila,Aram de Haas,Laetitia Wehry,Louis Boon,Reina E Mebius,Nadine van Montfoort,Manfred Wuhrer,Joke M M den Haan,Sandra J van Vliet,Yvette van Kooyk
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Despite the successful application of immune checkpoint blockade in a range of human cancers, immunotherapy in PDAC remains unsuccessful. PDAC is characterized by a desmoplastic, hypoxic and highly immunosuppressive tumor microenvironment (TME), where T-cell infiltration is often lacking (immune desert), or where T
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MDR1-EXPRESSING CD4+ T CELLS WITH TH1.17 FEATURES RESIST TO NEOADJUVANT CHEMOTHERAPY AND ARE ASSOCIATED WITH BREAST CANCER CLINICAL RESPONSE. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-01 Anthony Di Roio,Margaux Hubert,Laurie Besson,Marion Bossennec,Céline Rodriguez,Yenkel Grinberg-Bleyer,Guilhem Lalle,Lyvia Moudombi,Raphael Schneider,Cyril Degletagne,Isabelle Treilleux,Daniel J Campbell,Séverine Metzger,Thomas Duhen,Olivier Trédan,Christophe Caux,Christine Ménétrier-Caux
BACKGROUND Multidrug resistance-1 (MDR1) transporter limits the intracellular accumulation of chemotherapies (paclitaxel, anthracyclines) used in breast cancer (BC) treatment. In addition to tumor cells, MDR1 is expressed on immune cell subsets in which it confers chemoresistance. Among human T cells, MDR1 is expressed by most CD8+ T cells, and a subset of CD4+ T helper (Th) cells. Here we explored
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Cytoplasmic-delivery of polyinosine-polycytidylic acid inhibits pancreatic cancer progression increasing survival by activating Stat1-CCL2-mediated immunity. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-01 Praveen Bhoopathi,Amit Kumar,Anjan K Pradhan,Santanu Maji,Padmanabhan Mannangatti,Jolene J Windle,Mark A Subler,Dongyu Zhang,Vignesh Vudatha,Jose G Trevino,Esha Madan,Azeddine Atfi,Devanand Sarkar,Rajan Gogna,Swadesh K Das,Luni Emdad,Paul B Fisher
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer without effective therapies and with poor prognosis, causing 7% of all cancer-related fatalities in the USA. Considering the lack of effective therapies for this aggressive cancer, there is an urgent need to define newer and more effective therapeutic strategies. Polyinosine-polycytidylic acid (pIC) is a synthetic double-stranded
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Targeting myeloid checkpoint Siglec-10 reactivates antitumor immunity and improves anti-programmed cell death 1 efficacy in gastric cancer. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-01 Kunpeng Lv,Mengyao Sun,Hanji Fang,Jieti Wang,Chao Lin,Hao Liu,Heng Zhang,He Li,Hongyong He,Yun Gu,Ruochen Li,Fei Shao,Jiejie Xu
OBJECTIVE Immunotherapy has not yielded satisfactory therapeutic responses in gastric cancer (GC). However, targeting myeloid checkpoints holds promise for expanding the potential of immunotherapy. This study aims to evaluate the critical role of Siglec-10+ tumor-associated macrophages (TAMs) in regulating antitumor immunity and to explore the potential of the myeloid checkpoint Siglec-10 as an interventional
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Comprehensive analyses of immune tumor microenvironment in papillary renal cell carcinoma. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-01 Manon de Vries-Brilland,Nathalie Rioux-Leclercq,Maxime Meylan,Jonathan Dauvé,Christophe Passot,Elena Spirina-Menand,Ronan Flippot,Gaëlle Fromont,Gwenaelle Gravis,Lionnel Geoffrois,Christine Chevreau,Fréderic Rolland,Ellen Blanc,Félix Lefort,Alain Ravaud,Marine Gross-Goupil,Bernard Escudier,Sylvie Negrier,Laurence Albiges
BACKGROUND Papillary renal cell carcinoma (pRCC) is the most common non-clear cell RCC, and associated with poor outcomes in the metastatic setting. In this study, we aimed to comprehensively evaluate the immune tumor microenvironment (TME), largely unknown, of patients with metastatic pRCC and identify potential therapeutic targets. METHODS We performed quantitative gene expression analysis of TME
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Loss of ADAR1 in macrophages in combination with interferon gamma suppresses tumor growth by remodeling the tumor microenvironment. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-01 Weiwei Lin,Yikai Luo,Jie Wu,Haowan Zhang,Ge Jin,Chahua Guo,Hang Zhou,Han Liang,Xiaoyan Xu
BACKGROUND ADAR1, the major enzyme for RNA editing, has emerged as a tumor-intrinsic key determinant for cancer immunotherapy efficacy through modulating interferon-mediated innate immunity. However, the role of ADAR1 in innate immune cells such as macrophages remains unknown. METHODS We first analyzed publicly accessible patient-derived single-cell RNA-sequencing and perturbed RNA sequencing data
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Intraperitoneal administration of a modified vaccinia virus Ankara confers single-chain interleukin-12 expression to the omentum and achieves immune-mediated efficacy against peritoneal carcinomatosis. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-01 Ángela Bella,Leire Arrizabalaga,Claudia Augusta Di Trani,Jose Gonzalez-Gomariz,Celia Gomar,Joan Salvador Russo-Cabrera,Irene Olivera,Assunta Cirella,Myriam Fernandez-Sendin,Maite Alvarez,Alvaro Teijeira,Cigdem Atay,José Medina-Echeverz,Maria Hinterberger,Hubertus Hochrein,Ignacio Melero,Pedro Berraondo,Fernando Aranda
BACKGROUND Peritoneal carcinomatosis is an advanced stage of cancer in which the disease has spread to the peritoneal cavity. In order to restore antitumor immunity subverted by tumor cells in this location, we evaluated intraperitoneal administrations of modified vaccinia virus Ankara (MVA) engineered to express single-chain interleukin 12 (scIL-12) to increase antitumor immune responses. METHODS
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Th17-inducing dendritic cell vaccines stimulate effective CD4 T cell-dependent antitumor immunity in ovarian cancer that overcomes resistance to immune checkpoint blockade. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-01 Yan Luo,Barath Shreeder,James W Jenkins,Huashan Shi,Purushottam Lamichhane,Kexun Zhou,Deborah A Bahr,Sophia Kurian,Katherine A Jones,Joshua I Daum,Navnita Dutta,Brian M Necela,Martin J Cannon,Matthew S Block,Keith L Knutson
BACKGROUND Ovarian cancer (OC), a highly lethal cancer in women, has a 48% 5-year overall survival rate. Prior studies link the presence of IL-17 and Th17 T cells in the tumor microenvironment to improved survival in OC patients. To determine if Th17-inducing vaccines are therapeutically effective in OC, we created a murine model of Th17-inducing dendritic cell (DC) (Th17-DC) vaccination generated
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Multi-institutional analysis of aneuploidy and outcomes to chemoradiation and durvalumab in stage III non-small cell lung cancer. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-01 Joao V Alessi,Adam Price,Allison L Richards,Biagio Ricciuti,Xinan Wang,Arielle Elkrief,Federica Pecci,Alessandro Di Federico,Malini M Gandhi,Emily S Lebow,Patricia Mae G Santos,Maria Thor,Andreas Rimner,Adam J Schoenfeld,Jamie E Chaft,Bruce E Johnson,Daniel R Gomez,Mark M Awad,Narek Shaverdian
There is a need to identify predictive biomarkers to guide treatment strategies in stage III non-small cell lung cancer (NSCLCs). In this multi-institutional cohort of 197 patients with stage III NSCLC treated with concurrent chemoradiation (cCRT) and durvalumab consolidation, we identify that low tumor aneuploidy is independently associated with prolonged progression-free survival (HR 0.63; p=0.03)
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Quantifying the impact of immunotherapy on RNA dynamics in cancer. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-01 Ieva Usaite,Dhruva Biswas,Krijn Dijkstra,Thomas Bk Watkins,Oriol Pich,Clare Puttick,Mihaela Angelova,Krupa Thakkar,Crispin Hiley,Nicolai Birkbak,Marleen Kok,Simone Zaccaria,Yin Wu,Kevin Litchfield,Charles Swanton,Nnennaya Kanu
BACKGROUND Checkpoint inhibitor (CPI) immunotherapies have provided durable clinical responses across a range of solid tumor types for some patients with cancer. Nonetheless, response rates to CPI vary greatly between cancer types. Resolving intratumor transcriptomic changes induced by CPI may improve our understanding of the mechanisms of sensitivity and resistance. METHODS We assembled a cohort of
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PER2 binding to HSP90 enhances immune response against oral squamous cell carcinoma by inhibiting IKK/NF-κB pathway and PD-L1 expression. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-11-01 Zhiwei Zhang,Deping Sun,Hong Tang,Jie Ren,Shilin Yin,Kai Yang
BACKGROUND Programmed death-ligand 1 (PD-L1) contributes to the immune escape of tumor cells and is a critical target for antitumor immunotherapy. However, the molecular mechanisms regulating PD-L1 expression remain unclear, hindering the development of effective therapies. Here we investigate the role and molecular mechanism of the core clock gene Period2 (PER2) in regulating PD-L1 expression and
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Cytosolic DNA accumulation promotes breast cancer immunogenicity via a STING-independent pathway. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 Jing Zhang,Hui Dai,Lei Huo,Jared K Burks,Daniel J McGrail,Shiaw-Yih Lin
BACKGROUND Immune checkpoint blockade (ICB) has revolutionized cancer treatment. However, ICB alone has demonstrated only benefit in a small subset of patients with breast cancer. Recent studies have shown that agents targeting DNA damage response improve the efficacy of ICB and promote cytosolic DNA accumulation. However, recent clinical trials have shown that these agents are associated with hematological
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First-in-human phase I/Ib study of NIZ985, a recombinant heterodimer of IL-15 and IL-15Rα, as a single agent and in combination with spartalizumab in patients with advanced and metastatic solid tumors. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 Rom Leidner,Kevin Conlon,Douglas G McNeel,Andrea Wang-Gillam,Sumati Gupta,Robert Wesolowski,Monica Chaudhari,Nadia Hassounah,Jong Bong Lee,Lang Ho Lee,Jessica A O'Keeffe,Nancy Lewis,George N Pavlakis,John A Thompson
BACKGROUND Preclinically, interleukin-15 (IL-15) monotherapy promotes antitumor immune responses, which are enhanced when IL-15 is used in combination with immune checkpoint inhibitors (ICIs). This first-in-human study investigated NIZ985, a recombinant heterodimer comprising physiologically active IL-15 and IL-15 receptor α, as monotherapy and in combination with spartalizumab, an anti-programmed
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Comparison of SP263 and 22C3 immunohistochemistry PD-L1 assays for clinical efficacy of adjuvant atezolizumab in non-small cell lung cancer: results from the randomized phase III IMpower010 trial. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 Caicun Zhou,Minu K Srivastava,Hao Xu,Enriqueta Felip,Heather Wakelee,Nasser Altorki,Martin Reck,Rüdiger Liersch,Anna Kryzhanivska,Satoshi Oizumi,Hiroshi Tanaka,John Hamm,Steven L McCune,Elizabeth Bennett,Barbara Gitlitz,Virginia McNally,Marcus Ballinger,Mark McCleland,Wei Zou,Meghna Das Thakur,Silvia Novello
BACKGROUND Tumor samples from the phase III IMpower010 study were used to compare two programmed death-ligand 1 (PD-L1) immunohistochemistry assays (VENTANA SP263 and Dako 22C3) for identification of PD-L1 patient subgroups (negative, positive, low, and high expression) and their predictive value for adjuvant atezolizumab compared with best supportive care (BSC) in resectable early-stage non-small
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Impact of Helicobacter pylori infection status on outcomes among patients with advanced gastric cancer treated with immune checkpoint inhibitors. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 Patrick T Magahis,Steven B Maron,Darren Cowzer,Stephanie King,Mark Schattner,Yelena Janjigian,David Faleck,Monika Laszkowska
BACKGROUND Gut microbiota composition can influence cancer immunotherapy response. Recent evidence suggests Helicobacter pylori infection may reduce immune checkpoint inhibitor (ICI) efficacy in lung cancer and melanoma, but thorough characterization of this association in patients with gastric cancer is lacking. We aimed to determine the impact of H. pylori on survival in this population. METHODS
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Patient-derived lymphoma spheroids integrating immune tumor microenvironment as preclinical follicular lymphoma models for personalized medicine. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 Carla Faria,Fabien Gava,Pauline Gravelle,Juan Garcia Valero,Celia Dobaño-López,Nathalie Van Acker,Cathy Quelen,Gael Jalowicki,Renaud Morin,Cédric Rossi,Jean-Michel Lagarde,Jean-Jacques Fournié,Loïc Ysebaert,Camille Laurent,Patricia Pérez-Galán,Christine Bezombes
BACKGROUND Follicular lymphoma (FL), the most common indolent non-Hodgkin's Lymphoma, is a heterogeneous disease and a paradigm of the contribution of immune tumor microenvironment to disease onset, progression, and therapy resistance. Patient-derived models are scarce and fail to reproduce immune phenotypes and therapeutic responses. METHODS To capture disease heterogeneity and microenvironment cues
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Longitudinal evaluation of the biodistribution and cellular internalization of the bispecific CD3xTRP1 antibody in syngeneic mouse tumor models. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 Gerwin Gerhard Wemke Sandker,Jim Middelburg,Evienne Wilbrink,Janneke Molkenboer-Kuenen,Erik Aarntzen,Thorbald van Hall,Sandra Heskamp
BACKGROUND CD3 bispecific antibodies (CD3-bsAbs) require binding of both a tumor-associated surface antigen and CD3 for their immunotherapeutic effect. Their efficacy is, therefore, influenced by the tumor uptake and the extracellular dose. To optimize their currently limited efficacy in solid tumors, increased understanding of their pharmacokinetics and in vivo internalization is needed. METHODS Here
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Current perspectives on mass spectrometry-based immunopeptidomics: the computational angle to tumor antigen discovery. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 Bing Zhang,Michal Bassani-Sternberg
Identification of tumor antigens presented by the human leucocyte antigen (HLA) molecules is essential for the design of effective and safe cancer immunotherapies that rely on T cell recognition and killing of tumor cells. Mass spectrometry (MS)-based immunopeptidomics enables high-throughput, direct identification of HLA-bound peptides from a variety of cell lines, tumor tissues, and healthy tissues
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FGF/FGFR genomic amplification as a predictive biomarker for immune checkpoint blockade resistance: a short report. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 Nicolas Roussot,Julie Lecuelle,Lorraine Dalens,Caroline Truntzer,Francois Ghiringhelli
A novel crosstalk between immunogenic and oncometabolic pathways triggered by T cell-released interferon-gamma (IFN-ɣ) has been recently identified. This IFN-ɣ-pyruvate kinase M2-β-catenin axis relies on fibroblast growth factor 2 (FGF2) signaling in tumor cells and leads to hyperprogressive disease on immune checkpoint blockade (ICB) in preclinical models. This result underlines how IFN-ɣ signaling
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PD-1-expressing macrophages and CD8 T cells are independent predictors of clinical benefit from PD-1 inhibition in advanced mesothelioma. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 Krisztian Homicsko,Panagiota Zygoura,Maxim Norkin,Stephanie Tissot,Nicholas Shakarishvili,Sanjay Popat,Alessandra Curioni-Fontecedro,Mary O'Brien,Anthony Pope,Riyaz Shah,Patricia Fisher,James Spicer,Amy Roy,David Gilligan,Sylvie Rusakiewicz,Ekaterina Fortis,Nesa Marti,Roswitha Kammler,Stephen P Finn,Georges Coukos,Urania Dafni,Solange Peters,Rolf A Stahel
BACKGROUND Few tissue biomarkers exist to date that could enrich patient with cancer populations to benefit from immune checkpoint blockade by programmed cell death protein 1/ligand-1 (PD-/L-1) inhibitors. PD-L1 expression has value in this context in some tumor types but is an imperfect predictor of clinical benefit. In malignant pleural mesothelioma, PD-L1 expression is not predictive of the benefit
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MCT4 blockade increases the efficacy of immune checkpoint blockade. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 Nathalie Babl,Sonja-Maria Decking,Florian Voll,Michael Althammer,Ada Sala-Hojman,Roberta Ferretti,Clarissa Korf,Christian Schmidl,Lisa Schmidleithner,Benedikt Nerb,Carina Matos,Gudrun E Koehl,Peter Siska,Christina Bruss,Fabian Kellermeier,Katja Dettmer,Peter J Oefner,Marvin Wichland,Ines Ugele,Christopher Bohr,Wolfgang Herr,Shivapriya Ramaswamy,Timo Heinrich,Christian Herhaus,Marina Kreutz,Kathrin
BACKGROUND & AIMS Intratumoral lactate accumulation and acidosis impair T-cell function and antitumor immunity. Interestingly, expression of the lactate transporter monocarboxylate transporter (MCT) 4, but not MCT1, turned out to be prognostic for the survival of patients with rectal cancer, indicating that single MCT4 blockade might be a promising strategy to overcome glycolysis-related therapy resistance
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Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) neutralization counteracts T cell immune evasion in breast cancer. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 Cristina Travelli,Giorgia Colombo,Martina Aliotta,Francesca Fagiani,Natalia Fava,Rita De Sanctis,Ambra A Grolla,Joe G N Garcia,Nausicaa Clemente,Paola Portararo,Massimo Costanza,Fabrizio Condorelli,Mario Paolo Colombo,Sabina Sangaletti,Armando A Genazzani
BACKGROUND Nicotinamide phosphoribosyltransferase (NAMPT) is a key intracellular enzyme that participates in nicotinamide adenine dinucleotide (NAD) homeostasis as well as a released cytokine (eNAMPT) that is elevated in inflammatory conditions and in cancer. In patients with breast cancer, circulating eNAMPT is elevated and its plasma levels correlate with prognosis and staging. In light of this,
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Modification of Lugano criteria by pre-infusion tumor kinetics improves early survival prediction for patients with lymphoma under chimeric antigen receptor T-cell therapy. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 Michael Winkelmann,Viktoria Blumenberg,Kai Rejeski,Christina Quell,Veit Bücklein,Maria Ingenerf,Marcus Unterrainer,Christian Schmidt,Franziska J Dekorsy,Peter Bartenstein,Jens Ricke,Michael von Bergwelt-Baildon,Marion Subklewe,Wolfgang G Kunz
BACKGROUND Chimeric antigen receptor T-cell therapy (CART) is effective for patients with refractory or relapsed lymphoma with prolongation of survival. We aimed to improve the prediction of Lugano criteria for overall survival (OS) at 30-day follow-up (FU1) by including the pre-infusion tumor growth rate (TGRpre-BL) and its early change to 30-day FU1 imaging (TGRpost-BL). METHODS Consecutive patients
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Divergent tumor and immune cell reprogramming underlying immunotherapy response and immune-related adverse events in lung squamous cell carcinoma. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 Minjiang Chen,Pengfei Ma,Yongchang Zhang,Dong Wang,Zhuang Yu,Yujie Fu,Xiaojing Zhao,Mengzhao Wang,Guanglei Zhuang,Ying Jing
BACKGROUND Lung squamous cell carcinoma (LUSC) remains a leading cause of cancer-related deaths with few therapeutic strategies. Immune checkpoint inhibitors (ICIs) have demonstrated promising efficacy in patients with LUSC. However, ICIs could also lead to a unique spectrum of immune-related adverse events (irAEs), which dampen the clinical outcome. In-depth characterization of the immune hallmarks
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AdvanTIG-105: a phase I dose escalation study of the anti-TIGIT monoclonal antibody ociperlimab in combination with tislelizumab in patients with advanced solid tumors. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 Sophia Frentzas,Steven Kao,Rang Gao,Hao Zheng,Ahsan Rizwan,Nageshwar Budha,Luz de la Hoz Pedroza,Wei Tan,Tarek Meniawy
BACKGROUND Ociperlimab, a novel, humanized monoclonal antibody (mAb), binds to T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) with high affinity and specificity. Tislelizumab is an anti-programmed cell death protein 1 mAb. We report results from a phase I, first-in-human, dose escalation study evaluating the safety, pharmacokinetics (PK)
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Vaccination with post-translational modified, homocitrullinated peptides induces CD8 T-cell responses that mediate antitumor immunity. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 Sabaria Shah,Katherine W Cook,Peter Symonds,Juliane Weißer,Anne Skinner,Abdullah Al Omari,Samantha J Paston,Ian Pike,Lindy G Durrant,Victoria A Brentville
BACKGROUND Post-translational modification of proteins has the potential to alter the ability of T cells to recognize major histocompatibility complex (MHC) class -I and class-II restricted antigens, thereby resulting in altered immune responses. One such modification is carbamylation (homocitrullination) that results in the formation of homocitrulline (Hcit) residues in a non-enzymatic reaction of
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Analysing the tumor transcriptome of prostate cancer to predict efficacy of Lu-PSMA therapy. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 Analena Handke,Claudia Kesch,Wolfgang Peter Fendler,Tugce Telli,Yang Liu,Alexander Hakansson,Elai Davicioni,Jason Hughes,Hong Song,Katharina Lueckerath,Ken Herrmann,Boris Hadaschik,Robert Seifert
RATIONALE 177Lu-PSMA ([177Lu]Lutetium-PSMA-617) therapy is an effective treatment option for patients with prostate specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer, but still shows a non-responder rate of approximately 30%. Combination regimes of programmed death-ligand 1 (PD-L1) inhibition and concomitant 177Lu-PSMA therapy have been proposed to increase the
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Phase II study of durvalumab and tremelimumab with front-line neoadjuvant chemotherapy in patients with advanced-stage ovarian cancer: primary analysis in the original cohort of KGOG3046/TRU-D. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 Junsik Park,Jung Bok Lee,Myong Cheol Lim,Byoung-Gie Kim,Jae-Weon Kim,Sunghoon Kim,Chel Hun Choi,Hee Seung Kim,Sang Yoon Park,Jung-Yun Lee,
BACKGROUND This study assessed the antitumor activity and safety of durvalumab plus tremelimumab combined with neoadjuvant chemotherapy (NAC) in patients newly diagnosed with advanced ovarian cancer. Here, we report the primary endpoint of the original cohort of the KGOG 3046/TRU-D study. METHODS In this investigator-initiated single-arm, phase II trial, patients with stage IIIC-IVB ovarian cancer
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Classification of the tumor immune microenvironment and associations with outcomes in patients with metastatic melanoma treated with immunotherapies. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 Nurudeen A Adegoke,Tuba N Gide,Yizhe Mao,Camelia Quek,Ellis Patrick,Matteo S Carlino,Serigne N Lo,Alexander Maxwell Menzies,Ines Pires da Silva,Ismael A Vergara,Georgina Long,Richard A Scolyer,James S Wilmott
BACKGROUND Tumor microenvironment (TME) characteristics are potential biomarkers of response to immune checkpoint inhibitors in metastatic melanoma. This study developed a method to perform unsupervised classification of TME of metastatic melanoma. METHODS We used multiplex immunohistochemical and quantitative pathology-derived assessment of immune cell compositions of intratumoral and peritumoral
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Pretreatment radiomic biomarker for immunotherapy responder prediction in stage IB-IV NSCLC (LCDigital-IO Study): a multicenter retrospective study. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 Shaowei Wu,Weijie Zhan,Lan Liu,Daipeng Xie,Lintong Yao,Henian Yao,Guoqing Liao,Luyu Huang,Yubo Zhou,Peimeng You,Zekai Huang,Qiaxuan Li,Bin Xu,Siyun Wang,Guangyi Wang,Dong-Kun Zhang,Guibin Qiao,Lawrence Wing-Chi Chan,Michael Lanuti,Haiyu Zhou
BACKGROUND The predictive efficacy of current biomarker of immune checkpoint inhibitors (ICIs) is not sufficient. This study investigated the causality between radiomic biomarkers and immunotherapy response status in patients with stage IB-IV non-small cell lung cancer (NSCLC), including its biological context for ICIs treatment response prediction. METHODS CT images from 319 patients with pretreatment
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Increased interleukin-6/C-reactive protein levels are associated with the upregulation of the adenosine pathway and serve as potential markers of therapeutic resistance to immune checkpoint inhibitor-based therapies in non-small cell lung cancer. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 Abdul Rafeh Naqash,Justin D McCallen,Emma Mi,Sanna Iivanainen,Mona A Marie,Daria Gramenitskaya,James Clark,Jussi Pekka Koivunen,Shravanti Macherla,Sweta Jonnalagadda,Shanker Polsani,Rahim Ali Jiwani,Maida Hafiz,Mahvish Muzaffar,Leonardo Brunetti,Chipman R G Stroud,Paul R Walker,Kun Wang,Youngmin Chung,Eytan Ruppin,Se-Hoon Lee,Li V Yang,David J Pinato,Joo Sang Lee,Alessio Cortellini
BACKGROUND Systemic immune activation, hallmarked by C-reactive protein (CRP) and interleukin-6 (IL-6), can modulate antitumor immune responses. In this study, we evaluated the role of IL-6 and CRP in the stratification of patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). We also interrogated the underlying immunosuppressive mechanisms driven by the
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Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of melanoma, version 3.0. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 Anna C Pavlick,Charlotte E Ariyan,Elizabeth I Buchbinder,Diwakar Davar,Geoffrey T Gibney,Omid Hamid,Tina J Hieken,Benjamin Izar,Douglas B Johnson,Rajan P Kulkarni,Jason J Luke,Tara C Mitchell,Meghan J Mooradian,Krista M Rubin,April Ks Salama,Keisuke Shirai,Janis M Taube,Hussein A Tawbi,J Keith Tolley,Caressa Valdueza,Sarah A Weiss,Michael K Wong,Ryan J Sullivan
Since the first approval for immune checkpoint inhibitors (ICIs) for the treatment of cutaneous melanoma more than a decade ago, immunotherapy has completely transformed the treatment landscape of this chemotherapy-resistant disease. Combination regimens including ICIs directed against programmed cell death protein 1 (PD-1) with anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) agents or, more recently
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Adjuvant therapy in completely resected, EGFR-mutant non-small cell lung cancer: a comparative analysis of treatment efficacy between EGFR-TKI and anti-PD-1/PD-L1 immunotherapy. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 Zichun Li,Xuanye Zhang,Yuhong Wang,Zhixin Yu,Chunlong Yang,Yixin Zhou,Shaodong Hong
The IMpower010 and KEYNOTE-091 trials have demonstrated the benefit of adjuvant immunotherapy (IO) after chemotherapy (C+IO) in resected non-small cell lung cancer (NSCLC), including those with epidermal growth factor receptor gene (EGFR) mutation. Meanwhile, several studies have reported that EGFR-tyrosine kinase inhibitor (EGFR-TKI) may prolong disease-free survival (DFS) in these patients. However
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Efficacy and safety of cosibelimab, an anti-PD-L1 antibody, in metastatic cutaneous squamous cell carcinoma. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 Philip Clingan,Rahul Ladwa,Daniel Brungs,Dean Laurence Harris,Margaret McGrath,Susan Arnold,Jermaine Coward,Samuel Fourie,Andriy Kurochkin,Daniel R Malan,Andrew Mant,Vinay Sharma,Hong Shue,Andrea Tazbirkova,Miguel-Angel Berciano-Guerrero,Chaiyut Charoentum,Stéphane Dalle,Arunee Dechaphunkul,Oleksandr Dudnichenko,Piotr Koralewski,Iwona Lugowska,Henri Montaudié,Eva Muñoz-Couselo,Virote Sriuranpong,James
BACKGROUND Programmed cell death receptor-1 (PD-1)-blocking antibodies are approved to treat metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) cases ineligible for curative surgery or radiation. Notwithstanding, some patients experience inadequate responses or severe immune-related adverse events (AEs), indicating the need for improved therapies. Cosibelimab is a high-affinity
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Asymmetric anti-CLL-1×CD3 bispecific antibody, ABL602 2+1, with attenuated CD3 affinity endows potent antitumor activity but limited cytokine release. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 Eunhee Lee,Shinai Lee,Sumyeong Park,Yong-Gyu Son,Jiseon Yoo,Youngil Koh,Dong-Yeop Shin,Yangmi Lim,Jonghwa Won
BACKGROUND Acute myeloid leukemia (AML) is a type of leukemia in adults with a high mortality rate and poor prognosis. Although targeted therapeutics, chemotherapy, and hematopoietic stem cell transplantation can improve the prognosis, the recurrence rate is still high, with a 5-year survival rate of approximately 40%. This study aimed to develop an IgG-based asymmetric bispecific antibody that targets
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C-reactive protein impairs immune response of CD8+ T cells via FcγRIIb-p38MAPK-ROS axis in multiple myeloma. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 Jinxing Jiang,Ziyi Peng,Junying Wang,Mengping Chen,Yike Wan,Honghui Huang,Zhiqiang Liu,Jingya Wang,Jian Hou
BACKGROUND C-reactive protein (CRP) is a prototypical acute phase protein in humans with the function of regulating immune cells. Serum CRP levels are elevated in multiple myeloma (MM), associated with MM cell proliferation and bone destruction. However, its direct effects on T lymphocytes in MM have not been elucidated. METHODS Public data sets were used to explore the correlation of CRP levels with
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Neoantigen-specific CD4+ tumor-infiltrating lymphocytes are potent effectors identified within adoptive cell therapy products for metastatic melanoma patients. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 MacLean S Hall,Jamie K Teer,Xiaoqing Yu,Holly Branthoover,Sebastian Snedal,Madeline Rodriguez-Valentin,Luz Nagle,Ellen Scott,Ben Schachner,Patrick Innamarato,Amy M Hall,Jamie Blauvelt,Carolyn J Rich,Allison D Richards,Jake Ceccarelli,T J Langer,Sean J Yoder,Matthew S Beatty,Cheryl A Cox,Jane L Messina,Daniel Abate-Daga,James J Mule,John E Mullinax,Amod A Sarnaik,Shari Pilon-Thomas
BACKGROUND Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) is a promising immunotherapeutic approach for patients with advanced solid tumors. While numerous advances have been made, the contribution of neoantigen-specific CD4+T cells within TIL infusion products remains underexplored and therefore offers a significant opportunity for progress. METHODS We analyzed infused TIL
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Bladder cancer intrinsic LRFN2 drives anticancer immunotherapy resistance by attenuating CD8+ T cell infiltration and functional transition. J. Immunotherapy Cancer (IF 10.9) Pub Date : 2023-10-01 Anze Yu,Jiao Hu,Liangmin Fu,Gaowei Huang,Dingshan Deng,Mingxiao Zhang,Yinghan Wang,Guannan Shu,Lanyu Jing,Huihuang Li,Xu Chen,Taowei Yang,Jinhuan Wei,Zhenhua Chen,Xiongbing Zu,Junhang Luo
BACKGROUND Immune checkpoint inhibitor (ICI) therapy improves the survival of patients with advanced bladder cancer (BLCA); however, its overall effectiveness is limited, and many patients still develop immunotherapy resistance. The leucine-rich repeat and fibronectin type-III domain-containing protein (LRFN) family has previously been implicated in regulating brain dysfunction; however, the mechanisms