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  • Deciphering the immunomodulatory capacity of oncolytic vaccinia virus to enhance the immune response to breast cancer.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-04-07
    Brittany A Umer,Ryan S Noyce,Brian C Franczak,Mira M Shenouda,Rees G Kelly,Nicole A Favis,Megan Desaulniers,Troy A Baldwin,Mary M Hitt,David H Evans

    Vaccinia virus (VACV) is a double stranded DNA virus that devotes a large portion of its 200 Kbp genome to suppressing and manipulating the immune response of its host. Here, we investigated how targeted removal of immunomodulatory genes from the VACV genome impacted immune cells in the tumor microenvironment with the intention of improving the therapeutic efficacy of VACV in breast cancer. We performed

    更新日期:2020-04-08
  • Remodeling Translation Primes CD8+ T Cell Antitumor Immunity.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-04-07
    Katie E Hurst,Kiley A Lawrence,Rob A Robino,Lauren E Ball,Dongjun Chung,Jessica E Thaxton

    The requisites for protein translation in T cells are poorly understood and how translation shapes the antitumor efficacy of T cells is unknown. Here we demonstrated that IL15-conditioned T cells were primed by the metabolic energy sensor AMPK to undergo diminished translation relative to effector T cells. However, we showed that IL15-conditioned T cells exhibited a remarkable capacity to enhance their

    更新日期:2020-04-08
  • GITR agonism triggers antitumor immune responses through IL21-expressing follicular helper T cells.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-04-07
    Choong-Hyun Koh,Il-Kyu Kim,Kwang-Soo Shin,Insu Jeon,Boyeong Song,Jeong-Mi Lee,Eun-Ah Bae,Hyungseok Seo,Tae-Seung Kang,Byung-Seok Kim,Yeonseok Chung,Chang-Yuil Kang

    Although treatment with the glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) agonistic antibody (DTA-1) has shown antitumor activity in various tumor models, the underlying mechanism is not fully understood. Here, we demonstrate that interleukin (IL)-21-producing follicular helper T (Tfh) cells play a crucial role in DTA-1-induced tumor inhibition. The administration of

    更新日期:2020-04-08
  • CD226hiCD8+ T cells are a prerequisite for anti-TIGIT immunotherapy
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-04-07
    Hyung-seung Jin; Minkyung Ko; Da-som Choi; June Hyuck Kim; Dong-hee Lee; Seong-Ho Kang; Inki Kim; Hee Jin Lee; Eun Kyung Choi; Kyu-pyo Kim; Changhoon Yoo; Yoon Park

    Clinical trials are evaluating the efficacy of anti-TIGIT for use as single-agent therapy or in combination with PD-1/PD-L1 blockade. How and whether a TIGIT blockade will synergize with immunotherapies is not clear. Here we show that CD226loCD8+ T cells accumulate at the tumor site and have an exhausted phenotype with impaired functionality. In contrast, CD226hiCD8+ tumor-infiltrating T cells possess

    更新日期:2020-04-08
  • Verteporfin inhibits PD-L1 through autophagy and the STAT1-IRF1-TRIM28 signaling axis, exerting antitumor efficacy
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-04-07
    Jiyong Liang; Lulu Wang; Chao Wang; Jianfeng Shen; Bojin Su; Anantha Marisetty; Dexing Fang; Cynthia Kassab; Kang Jin Jeong; Wei Zhao; Yiling Lu; Abhinav K Jain; Zhicheng Zhou; Han Liang; Shao-Cong Sun; Changming Lu; Zhi-Xiang Xu; Qinghua Yu; Shan Shao; Xiaohua Chen; Meng Gao; Francois X. Claret; Zhiyong Ding; Jian Chen; Pingsheng Chen; Michelle C. Barton; Guang Peng; Gordon B. Mills; Amy B Heimberger

    PD-L1 (programmed cell death 1 ligand 1) is a key driver of tumor-mediated immune suppression and targeting it with antibodies can induce therapeutic responses. Given the costs and associated toxicity of PD-L1 blockade, alternative therapeutic strategies are needed. Using reverse-phase protein arrays to assess drugs in use or likely to enter trials, we performed a candidate drug screen for inhibitors

    更新日期:2020-04-08
  • A Sampling of Highlights from the Literature
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-04-01
    American Association for Cancer Research

    ![][1] [ Another unusual recognition system (from piqsels.com) ][2] γδ T cells are essential for immunity. Human Vγ9Vδ2 T cells recognize phosphoantigens (pAgs) from microbes and tumors in an MHC-unrestricted manner. Activation induces inflammatory cytokine release and cytolytic

    更新日期:2020-04-01
  • Immune Escape during Breast Tumor Progression
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-04-01
    Carlos R. Gil Del Alcazar; Maša Alečković; Kornelia Polyak

    Immunotherapy using checkpoint inhibitors is one of the most promising current cancer treatment strategies. However, in breast cancer, its success has been limited to a subset of patients with triple-negative disease, whose durability of observed responses remain unclear. The lack of detailed understanding of breast tumor immune evasion mechanisms and the treatment of patients with highly heterogeneous

    更新日期:2020-04-01
  • Inhibition of the SRC Kinase HCK Impairs STAT3-Dependent Gastric Tumor Growth in Mice.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-04-01
    Ashleigh R Poh,Amy R Dwyer,Moritz F Eissmann,Ashwini L Chand,David Baloyan,Louis Boon,Michael W Murrey,Lachlan Whitehead,Megan O'Brien,Clifford A Lowell,Tracy L Putoczki,Fiona J Pixley,Robert J J O'Donoghue,Matthias Ernst

    Persistent activation of the latent transcription factor STAT3 is observed in gastric tumor epithelial and immune cells and is associated with a poor patient prognosis. Although targeting STAT3-activating upstream kinases offers therapeutically viable targets with limited specificity, direct inhibition of STAT3 remains challenging. Here we provide functional evidence that myeloid-specific hematopoietic

    更新日期:2020-04-01
  • Cancer-associated fibroblasts promote immunosuppression by inducing ROS-generating monocytic MDSCs in lung squamous cell carcinoma.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-04-01
    Handan Xiang,Carlo P Ramil,Josephine Hai,Chunsheng Zhang,Huijun Wang,Amanda A Watkins,Roshi Afshar,Peter Georgiev,Marc A Sze,Xuelei S Song,Patrick J Curran,Mangeng Cheng,J Richard Miller,Dongyu Sun,Andrey Loboda,Yanlin Jia,Lily Y Moy,An Chi,Philip E Brandish

    Cancer-associated fibroblasts (CAFs) represent a functionally heterogenous population of activated fibroblasts that constitutes a major component of tumor stroma. Although CAFs have been shown to promote tumor growth and mediate resistance to chemotherapy, the mechanisms by which they may contribute to immune suppression within the tumor microenvironment (TME) in lung squamous cell carcinoma (LSCC)

    更新日期:2020-04-01
  • Interferon-induced IDO1 mediates radiation resistance and is a therapeutic target in colorectal cancer.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-04-01
    Baosheng Chen,David M Alvarado,Micah Iticovici,Nathan S Kau,Haeseong Park,Parag J Parikh,Dinesh Thotala,Matthew A Ciorba

    Colorectal cancer (CRC) is a major cause of mortality worldwide. Chemotherapy and radiation remain standard treatment for locally advanced disease, with current immune-targeting therapies applying to only a small subset of patients. Expression of the immuno-oncology target indoleamine 2,3 dioxygenase 1 (IDO1) is associated with poor CRC clinical outcomes but is understudied as a potential treatment

    更新日期:2020-04-01
  • CD73 blockade promotes dendritic cell infiltration of irradiated tumors and tumor rejection.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-04-01
    Erik Wennerberg,Sheila Spada,Nils-Petter Rudqvist,Claire Lhuillier,Sylvia Gruber,Qiuying Chen,Fengli Zhang,Xi K Zhou,Steven S Gross,Silvia C Formenti,Sandra Demaria

    The ability of focal radiotherapy to promote priming of tumor-specific CD8+ T cells and increase responses to immunotherapy is dependent on infiltration of the tumor by Batf3-dependent conventional dendritic cell type 1 (cDC1) cells. Such infiltration is driven by radiotherapy-induced IFN type I (IFN-I). Other signals may also modulate cDC1 infiltration of irradiated tumors. Here we found increased

    更新日期:2020-04-01
  • Fatty acid oxidation controls CD8+ tissue-resident memory T cell survival in gastric adenocarcinoma.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-04-01
    Run Lin,Hui Zhang,Yujie Yuan,Qiong He,Jianwen Zhou,Shuhua Li,Yu Sun,Daniel Y Li,Hai-Bo Qiu,Wei Wang,Zhehong Zhuang,Bin Chen,Yonghui Huang,Chuwei Liu,Yingzhao Wang,Shirong Cai,Zunfu Ke,Weiling He

    The success of checkpoint inhibitors in cancer treatment is associated with the infiltration of tissue-resident memory T cells (Trm). In this study, we found that about 30% of tumor infiltrating lymphocytes (TILs) in TME of gastric adenocarcinoma (GAC) were CD69+CD103+ Trm cells. Trm cells were low in patients with metastasis and the presence of Trm cells was associated with better prognosis in GAC

    更新日期:2020-04-01
  • Metabolome of Pancreatic Juice Delineates Distinct Clinical Profiles of Pancreatic Cancer and Reveals a Link between Glucose Metabolism and PD-1+ Cells.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-04-01
    Nina Cortese,Giovanni Capretti,Marialuisa Barbagallo,Alessandra Rigamonti,Panteleimon G Takis,Giovanni F Castino,Debora Vignali,Giulia Maggi,Francesca Gavazzi,Cristina Ridolfi,Gennaro Nappo,Greta Donisi,Marco Erreni,Roberta Avigni,Daoud Rahal,Paola Spaggiari,Massimo Roncalli,Paola Cappello,Francesco Novelli,Paolo Monti,Alessandro Zerbi,Paola Allavena,Alberto Mantovani,Federica Marchesi

    Better understanding of pancreatic diseases, including pancreatic ductal adenocarcinoma (PDAC), is an urgent medical need, with little advances in preoperative differential diagnosis, preventing rational selection of therapeutic strategies. The clinical management of pancreatic cancer patients would benefit from the identification of variables distinctively associated with the multiplicity of pancreatic

    更新日期:2020-04-01
  • Inhibition of SHP-1 expands the repertoire of antitumor T cells available to respond to immune checkpoint blockade.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-04-01
    Jeremy P Snook,Ashleigh J Soedel,H Atakan Ekiz,Ryan M O'Connell,Matthew A Williams

    The presence and activity of CD8+ T cells within the tumor microenvironment is essential for the control of tumor growth. Utilizing B16-F10 melanoma tumors that express altered peptide ligands of chicken ovalbumin, OVA257-264, we measured high- and low-affinity OVA-specific responses following adoptive transfer of OT-I CD8+ T cell into mice subsequently challenged with tumors. TCR affinity positively

    更新日期:2020-04-01
  • Improved Antitumor Efficacy of Chimeric Antigen Receptor T Cells that Secrete Single-Domain Antibody Fragments.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-04-01
    Yushu Joy Xie,Michael Dougan,Jessica R Ingram,Novalia Pishesha,Tao Fang,Noor Momin,Hidde L Ploegh

    Chimeric antigen receptor (CAR) T-cell therapy is effective in the treatment of cancers of hematopoietic origin. In the immunosuppressive solid tumor environment, CAR T cells encounter obstacles that compromise their efficacy. We developed a strategy to address these barriers by having CAR T cells secrete single-domain antibody fragments [variable heavy domain of heavy chain antibodies (VHH) or nanobodies]

    更新日期:2020-04-01
  • γδ T-cell receptors derived from breast cancer-infiltrating T lymphocytes mediate antitumor reactivity.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-04-01
    Anke Janssen,José Villacorta Hidalgo,Dennis X Beringer,Sanne van Dooremalen,Febilla Fernando,Eline van Diest,Antonela R Terrizzi,Peter Bronsert,Sylvia Kock,Annette Schmitt-Graeff,Martin Werner,Kerstin Heise,Marie Follo,Trudy Straetemans,Zsolt Sebestyen,Dmitriy M Chudakov,Sofya A Kasatskaya,Felix E Frenkel,Sarina Ravens,Eric Spierings,Immo Prinz,Ralf Küppers,Miroslav Malkovsky,Paul Fisch,Jurgen Kuball

    γδ T cells in human solid tumors remain poorly defined. Here, we describe molecular and functional analyses of T-cell receptors (TCRs) from tumor-infiltrating γδ T lymphocytes (γδ TILs) that were in direct contact with tumor cells in breast cancer lesions from archival material. We observed that the majority of γδ TILs harbored a proinflammatory phenotype and only a minority associated with the expression

    更新日期:2020-04-01
  • Proteogenomics uncovers a vast repertoire of shared tumor-specific antigens in ovarian cancer.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-04-01
    Qingchuan Zhao,Jean-Philippe Laverdure,Joel Lanoix,Chantal Durette,Caroline Coté,Eric Bonneil,Céline M Laumont,Patrick Gendron,Krystel Vincent,Mathieu Courcelles,Sébastien Lemieux,Douglas G Millar,Pamela S Ohashi,Pierre Thibault,Claude Perreault

    High-grade serous ovarian cancer (HGSC), the principal cause of death from gynecological malignancies in the world, has not significantly benefited from advances in cancer immunotherapy. Although HGSC infiltration by lymphocytes correlates with superior survival, the nature of antigens that can elicit anti-HGSC immune responses is unknown. The goal of this study was to establish the global landscape

    更新日期:2020-04-01
  • Immunosuppressive Mediators Impair Proinflammatory Innate Lymphoid Cell Function in Human Malignant Melanoma.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-04-01
    Giuseppe Ercolano,Andrea Garcia-Garijo,Bérengère Salomé,Alejandra Gomez-Cadena,Giulia Vanoni,Beatris Mastelic-Gavillet,Angela Ianaro,Daniel E Speiser,Pedro Romero,Sara Trabanelli,Camilla Jandus

    Innate lymphoid cells (ILC) are a family of immune cells that are emerging as potent orchestrators of immune responses. In cancer, ILCs display both pro- and antitumorigenic functions depending on the nature of the tumor and the involved ILC subset. Little is known about the ILC-tumor cross-talk in human melanoma. Here, we showed that ILC1s were enriched but functionally impaired in cytokine secretion

    更新日期:2020-04-01
  • LncRNA AK036396 inhibits maturation and accelerates immunosuppression of polymorphonuclear myeloid-derived suppressor cells by enhancing the stability of ficolin B.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-04-01
    Xinyu Tian,Yu Zheng,Kai Yin,Jie Ma,Jie Tian,Yue Zhang,Lingxiang Mao,Huaxi Xu,Shengjun Wang

    Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of cell biology. However, the role of lncRNAs in the development and function of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) remains unclear. Here, we identified that the lncRNA AK036396 was highly expressed in PMN-MDSCs, and lncRNA AK036396 knockdown promoted the maturation and decreased the suppressive function of

    更新日期:2020-04-01
  • Anti-VEGF Treatment Enhances CD8+ T-Cell Antitumor Activity by Amplifying Hypoxia
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-04-01
    Patricia E de Almeida; Judy Mak; Genevive Hernandez; Rajiv Jesudason; Aurelie Herault; Vincent Javinal; Jovencio Borneo; Jeong M Kim; Kevin Barry Walsh

    Anti-angiogenic therapies that target the vascular endothelial growth factor (VEGF) pathway have been used clinically to combat cancer for over a decade. Beyond having a direct impact on blood vessel development and tumor perfusion, accumulating evidence indicates that these agents also affect antitumor immune responses. Numerous clinical trials combining anti-angiogenic drugs with immunotherapies

    更新日期:2020-04-01
  • CSF1R is required for differentiation and migration of Langerhans cells and Langerhans cell histiocytosis
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-04-01
    Silvia Lonardi; Sara Scutera; Sara Licini; Luisa Lorenzi; Anna Maria Cesinaro; Luisa Benerini Gatta; Carlotta Castagnoli; Daniele Bollero; Rosaria Sparti; Michela Tomaselli; Daniela Medicina; Federica Calzetti; Marco A Cassatella; Fabio Facchetti; Tiziana Musso; William Vermi

    Langerhans cell histiocytosis (LCH) is a rare disorder characterized by tissue accumulation of CD1a+ CD207+ LCH cells. In LCH, somatic mutations of the BRAFV600E gene have been detected in tissue LCH cells, bone marrow CD34+ hematopoietic stem cells, circulating CD14+ monocytes, and BDCA1+ myeloid DCs. Targeting BRAFV600E in clonal LCs and their precursors is a potential treatment option for patients

    更新日期:2020-04-01
  • Quantification of Early-Stage Myeloid-Derived Suppressor Cells in Cancer Requires Excluding Basophils
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-04-01
    ANM Nazmul H. Khan; Tiffany R Emmons; Jerry T. Wong; Emad Alqassim; Kelly L Singel; Jaron Mark; Brandon E Smith; Joseph D. Tario; Kevin H. Eng; Kirsten B. Moysich; Kunle Odunsi; Scott I. Abrams; Brahm H Segal

    Myeloid derived suppressor cells (MDSCs) are a heterogeneous group of immature cells that accumulate in the peripheral blood and tumor microenvironment and are barriers to cancer therapy. MDSCs serve as prognostic biomarkers and are targets for therapy. Based on surface markers, three subsets of MDSCs have been defined in humans: granulocytic, monocytic and early-stage (e-MDSCs). The markers attributed

    更新日期:2020-04-01
  • Human NKp44+ group 3 innate lymphoid cells associate with tumor-associated tertiary lymphoid structures in colorectal cancer
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-03-30
    Atsuyo Ikeda; Takayuki Ogino; Hisako Kayama; Daisuke Okuzaki; Junichi Nishimura; Shiki Fujino; Norikatsu Miyoshi; Hidekazu Takahashi; Mamoru Uemura; Chu Matsuda; Hirofumi Yamamoto; Kiyoshi Takeda; Tsunekazu Mizushima; Masaki Mori; Yuichiro Doki

    Innate lymphoid cells (ILCs) are responsible for mucosal tissue homeostasis and are involved in the progression and suppression of several types of cancer. However, the effects of ILCs on colorectal cancer (CRC) are poorly understood. We characterized human ILCs in normal colon and CRC tissue, investigating their role in the tumor immune microenvironment. Normal mucosa and tumor tissues were obtained

    更新日期:2020-03-31
  • Histone deacetylase inhibitors and IL21 cooperate to reprogram human effector CD8+ T cells to memory T cells
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-03-25
    Junmei Wang; Farah Hasan; Amanda C Frey; Haiyan S. Li; Jungsun Park; Ke Pan; Cara Haymaker; Chantale Bernatchez; Dean A Lee; Stephanie S. Watowich; Cassian Yee

    Clinical response rates after adoptive cell therapy (ACT) are highly correlated with in vivo persistence of the infused T cells. However, antigen-specific T cells found in tumor sites are often well-differentiated effector cells with limited persistence. Central memory CD8+ T cells, capable of self-renewal, represent desirable ACT products. We report here that exposure to a histone deacetylase inhibitor

    更新日期:2020-03-26
  • Excessive costimulation leads to dysfunction of adoptively transferred T cells
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-03-25
    Dinali Wijewarnasuriya; Christina Bebernitz; Andrea V Lopez; Sarwish Rafiq; Renier J Brentjens

    Although clinical responses with CD19 targeting CAR T-cell treatment have been observed in patients with certain hematological malignancies, high rates of disease relapse highlight the necessity to understand and improve mechanisms of CAR T-cell failure. Since T-cell dysfunction is thought to contribute to CAR T-cell treatment failure, understanding what mechanisms drive T cells into this dysfunctional

    更新日期:2020-03-26
  • Donor lymphocyte-derived natural killer cells control major histocompatibility complex class I-negative melanoma
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-03-24
    Nana Dang; Yuan Lin; Mark Waer; Ben Sprangers

    Natural killer (NK) cells provide a natural defense against MHC-I-negative tumors, such as melanoma. Donor lymphocyte infusion (DLI) containing NK cells, a form of adoptive immunotherapy used after allogenic bone marrow transplantation (allo-BMT), promotes antitumor immune responses, but is often associated with life-threatening complications such as graft-versus host disease (GVHD). Here, we showed

    更新日期:2020-03-24
  • Optimization of T-cell receptor-modified T cells for cancer therapy
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-03-24
    Dylan J. Drakes; Sarwish Rafiq; Terence J Purdon; Andrea V Lopez; Smita S. Chandran; Christopher A. Klebanoff; Renier J Brentjens

    T-cell receptor (TCR)-modified T-cell gene therapy can target a variety of extracellular and intracellular tumor associated antigens, yet has had little clinical success. A potential explanation for limited antitumor efficacy is a lack of T-cell activation in vivo. We postulated that expression of pro-inflammatory cytokines in TCR-modified T cells would activate T cells and enhance antitumor efficacy

    更新日期:2020-03-24
  • Inhibition of MICA and MICB Shedding Elicits NK cell-mediated Immunity against Tumors Resistant to Cytotoxic T cells
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-03-24
    Lucas Ferrari de Andrade; Sushil Kumar; Adrienne Luoma; Yoshinaga Ito; Pedro Henrique Alves da Silva; Deng Pan; Jason W Pyrdol; Charles H. Yoon; Kai W Wucherpfennig

    Resistance to cytotoxic T cells is frequently mediated by loss of MHC class I expression or IFNγ signaling in tumor cells, such as mutations of B2M or JAK1 genes. NK cells could potentially target such resistant tumors, but suitable NK cell-based strategies remain to be developed. We hypothesized that such tumors could be targeted by NK cells if sufficient activating signals were provided. Human tumors

    更新日期:2020-03-24
  • Enhanced immunogenicity of mitochondrial-localized proteins in cancer cells
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-03-23
    Gennaro Prota; Uzi Gileadi; Margarida Rei; Ana Victoria Lechuga-Vieco; Ji-Li Chen; Silvia Galiani; Melissa Bedard; Vivian Wing Chong Lau; Lorenzo F Fanchi; Mara Artibani; Zhiyuan Hu; Siamon Gordon; Jan Rehwinkel; Jose A Enríquez; Ahmed A Ahmed; Ton N Schumacher; Vincenzo Cerundolo

    Epitopes derived from mutated cancer proteins elicit strong antitumor T-cell responses that correlate with clinical efficacy in a proportion of patients. However, it remains unclear whether the subcellular localization of mutated proteins influences the efficiency of T-cell priming. To address this question we compared the immunogenicity of NY-ESO-1 and OVA localized either in the cytosol or in mitochondria

    更新日期:2020-03-24
  • A PSMA-targeting CD3 bispecific antibody induces antitumor responses that are enhanced by 4-1BB costimulation
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-03-17
    Danica Chiu; Richard Tavaré; Lauric Haber; Olulanu H Aina; Kristin Vazzana; Priyanka Ram; Makenzie Danton; Jennifer Finney; Sumreen Jalal; Pamela Krueger; Jason T. Giurleo; Dangshe Ma; Eric Smith; Gavin Thurston; Jessica R. Kirshner; Alison Crawford

    Patients with hematological cancers have improved outcomes after treatment with bispecific antibodies that bind to CD3 on T cells and that redirect T cells towards cancer cells. However, clinical benefit against solid tumors remains to be shown. We made a bispecific antibody that targets both the common prostate tumor-specific antigen PSMA and CD3 (PMSAxCD3) and provide evidence for tumor inhibition

    更新日期:2020-03-19
  • Identification of the targets of T cell receptor therapeutic agents and cells by use of a high throughput genetic platform
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-03-17
    Ron S Gejman; Heather F Jones; Martin G Klatt; Aaron Y Chang; Claire Y Oh; Smita S. Chandran; Tatyana Korontsvit; Viktoriya Zakahleva; Tao Dao; Christopher A. Klebanoff; David A Scheinberg

    T cell receptor (TCR)-based therapeutic cells and agents have emerged as a new class of effective cancer therapies. These therapies work on cells that express intracellular cancer-associated proteins by targeting peptides displayed on major histocompatibility complex receptors. However, cross-reactivities of these agents to off-target cells and tissues have resulted in serious, sometimes fatal, adverse

    更新日期:2020-03-19
  • Prevalent and diverse intratumoral oncoprotein-specific CD8+ T cells within polyoma virus-driven Merkel cell carcinomas
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-03-16
    Lichen Jing; Mariliis Ott; Candice D Church; Rima M Kulikauskas; Dafina Ibrani; Jayasri G. Iyer; Olga K Afanasiev; Aric Colunga; Maclean M Cook; Hong Xie; Alexander L Greninger; Kelly G Paulson; Aude G Chapuis; Shailender Bhatia; Paul Nghiem; David M Koelle

    Merkel cell carcinoma (MCC) is often caused by persistent expression of Merkel cell polyomavirus (MCPyV) T-antigen (T-Ag). These non-self proteins comprise about 400 amino acids (AAs). Clinical responses to immune checkpoint inhibitors, seen in about half of patients, may relate to T-Ag-specific T cells. Strategies to increase CD8+ T-cell number, breadth, or function could augment checkpoint inhibition

    更新日期:2020-03-16
  • IL1α antagonizes IL1β and promotes adaptive immune rejection of malignant tumors
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-03-11
    Tian Tian; Serena Lofftus; Youdong Pan; Claire Anise Stingley; Sandra L King; Jingxia Zhao; Timothy Y Pan; Rebecca Lock; Jacob William Marglous; Kevin Liu; Hans R Widlund; Robert C Fuhlbrigge; Karen Cichowski; Thomas S. Kupper

    We assessed the contribution of interleukin-1 (IL1) signaling molecules to malignant tumor growth, using IL1β-/-, IL1α-/-, and IL1R1-/- mice. Tumors grew progressively in IL1R-/- and IL1α-/- mice, but were often absent in IL1β-/- mice. This was observed whether tumors were implanted intradermally or injected intravenously and was true across multiple distinct tumor lineages. Antibodies to IL1β prevented

    更新日期:2020-03-12
  • SINGLE-CELL IMMUNE COMPETENCY SIGNATURES ASSOCIATE WITH SURVIVAL IN PHASE 2 GVAX AND CRS-207 RANDOMIZED STUDIES IN METASTATIC PANCREATIC CANCER PATIENTS
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-03-04
    Nitya Nair; Shih-Yu Chen; Ed Lemmens; Serena Chang; Dung T. Le; Elizabeth M. Jaffee; Aimee Murphy; Chan Whiting; Thomas Müller; Dirk G Brockstedt

    The identification of biomarkers for patient stratification is fundamental to precision medicine efforts in oncology. Here, we identified two baseline, circulating immune cell subsets associated with overall survival in metastatic pancreatic cancer patients who were enrolled in two phase 2 randomized studies of GVAX pancreas and CRS-207 immunotherapy. Single-cell mass cytometry was used to simultaneously

    更新日期:2020-03-04
  • Intratumoral Delivery of a PD-1-blocking scFv encoded in Oncolytic HSV-1 Promotes Antitumor Immunity and Synergizes with TIGIT Blockade.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-03-03
    Chaolong Lin,Wenfeng Ren,Yong Luo,Shaopeng Li,Yating Chang,Lu Li,Dan Xiong,Xiaoxuan Huang,Zilong Xu,Zeng Yu,Yingbin Wang,Jun Zhang,Chenghao Huang,Ningshao Xia

    Oncolytic virotherapy can lead to systemic antitumor immunity, but the therapeutic potential of oncolytic viruses (OVs) in humans is limited due to their insufficient ability to overcome the immunosuppressive tumor microenvironment (TME). Here, we showed that locoregional oncolytic virotherapy upregulated the expression of PD-L1 in the TME, which was mediated by virus-induced type I and type II interferons

    更新日期:2020-03-03
  • A Sampling of Highlights from the Literature
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-03-01
    American Association for Cancer Research

    ![][1] [ More useful repurposing, from bootside to benchside (by Victorgrigas via Wikimedia Commons) ][2] Most tumors lack the infiltrating T cells associated with better outcomes and immunotherapy responses. Influenza infections, which create a hot environment in the lung, prolong

    更新日期:2020-03-02
  • Tumor Cell-Intrinsic USP22 Suppresses Antitumor Immunity in Pancreatic Cancer.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2019-12-23
    Jinyang Li,Salina Yuan,Robert J Norgard,Fangxue Yan,Taiji Yamazoe,Andrés Blanco,Ben Z Stanger

    Although immune checkpoint blockade (ICB) improves clinical outcome in several types of malignancies, pancreatic ductal adenocarcinoma (PDA) remains refractory to this therapy. Preclinical studies have demonstrated that the relative abundance of suppressive myeloid cells versus cytotoxic T cells determines the efficacy of combination immunotherapies, which include ICB. Here, we evaluated the role of

    更新日期:2020-03-02
  • B cell-Derived IL35 Drives STAT3-Dependent CD8+ T-cell Exclusion in Pancreatic Cancer.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-02-05
    Bhalchandra Mirlekar,Daniel Michaud,Samuel J Lee,Nancy P Kren,Cameron Harris,Kevin Greene,Emily C Goldman,Gaorav P Gupta,Ryan C Fields,William G Hawkins,David G DeNardo,Naim U Rashid,Jen Jen Yeh,Autumn J McRee,Benjamin G Vincent,Dario A A Vignali,Yuliya Pylayeva-Gupta

    Pancreatic ductal adenocarcinoma (PDA) is an aggressive malignancy characterized by a paucity of tumor-proximal CD8+ T cells and resistance to immunotherapeutic interventions. Cancer-associated mechanisms that elicit CD8+ T-cell exclusion and resistance to immunotherapy are not well-known. Here, using a Kras- and p53-driven model of PDA, we describe a mechanism of action for the protumorigenic cytokine

    更新日期:2020-03-02
  • Glypican-3-Specific CAR T Cells Coexpressing IL15 and IL21 Have Superior Expansion and Antitumor Activity against Hepatocellular Carcinoma.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-01-17
    Sai Arun Batra,Purva Rathi,Linjie Guo,Amy N Courtney,Julien Fleurence,Julien Balzeau,Rahamthulla S Shaik,Thao P Nguyen,Meng-Fen Wu,Shaun Bulsara,Maksim Mamonkin,Leonid S Metelitsa,Andras Heczey

    Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death in the world, and curative systemic therapies are lacking. Chimeric antigen receptor (CAR)-expressing T cells induce robust antitumor responses in patients with hematologic malignancies but have limited efficacy in patients with solid tumors, including HCC. IL15 and IL21 promote T-cell expansion, survival, and function

    更新日期:2020-03-02
  • IL6 Induces an IL22+ CD8+ T-cell Subset with Potent Antitumor Function.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-01-21
    Michael St Paul,Samuel D Saibil,Scott C Lien,SeongJun Han,Azin Sayad,David T Mulder,Carlos R Garcia-Batres,Alisha R Elford,Kavita Israni-Winger,Céline Robert-Tissot,Michael Zon,Sarah Rachel Katz,Patricia A Shaw,Blaise A Clarke,Marcus Q Bernardini,Linh T Nguyen,Benjamin Haibe-Kains,Trevor J Pugh,Pamela S Ohashi

    CD8+ T cells can be polarized into several different subsets as defined by the cytokines they produce and the transcription factors that govern their differentiation. Here, we identified the polarizing conditions to induce an IL22-producing CD8+ Tc22 subset, which is dependent on IL6 and the aryl hydrocarbon receptor transcription factor. Further characterization showed that this subset was highly

    更新日期:2020-03-02
  • CD4+ T-cell Immunity in the Peripheral Blood Correlates with Response to Anti-PD-1 Therapy.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2019-12-23
    Hiroshi Kagamu,Shigehisa Kitano,Ou Yamaguchi,Kenichi Yoshimura,Katsuhisa Horimoto,Masashi Kitazawa,Kazuhiko Fukui,Ayako Shiono,Atsuhito Mouri,Fuyumi Nishihara,Yu Miura,Kosuke Hashimoto,Yoshitake Murayama,Kyoichi Kaira,Kunihiko Kobayashi

    Accumulating evidence indicates that CD8+ T cells in the tumor microenvironment and systemic CD4+ T-cell immunity play an important role in mediating durable antitumor responses. We longitudinally examined T-cell immunity in the peripheral blood of patients with non-small lung cancer and found that responders had significantly (P < 0.0001) higher percentages of effector, CD62Llow CD4+ T cells prior

    更新日期:2020-03-02
  • Combined CD44- and CD25-Targeted Near-Infrared Photoimmunotherapy Selectively Kills Cancer and Regulatory T Cells in Syngeneic Mouse Cancer Models.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-01-17
    Yasuhiro Maruoka,Aki Furusawa,Ryuhei Okada,Fuyuki Inagaki,Daiki Fujimura,Hiroaki Wakiyama,Takuya Kato,Tadanobu Nagaya,Peter L Choyke,Hisataka Kobayashi

    Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed and selective cancer treatment that induces necrotic and immunogenic cell death and utilizes a mAb conjugated to a photo-absorber dye, IR700DX, activated by NIR light. Although CD44 is a surface cancer marker associated with drug resistance, anti-CD44-IR700 NIR-PIT results in inhibited cell growth and prolonged survival in multiple tumor

    更新日期:2020-03-02
  • Control of Metastases via Myeloid CD39 and NK Cell Effector Function.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-01-28
    Juming Yan,Xian-Yang Li,Amelia Roman Aguilera,Christos Xiao,Celia Jacoberger-Foissac,Bianca Nowlan,Simon C Robson,Courtney Beers,Achim K Moesta,Nishamol Geetha,Michele W L Teng,Mark J Smyth

    Natural killer (NK) cell protection from tumor metastases is a critical feature of the host immune response to cancer, but various immunosuppression mechanisms limit NK cell effector function. The ectoenzyme, CD39, expressed on tumor-infiltrating myeloid cells, granulocytes, and lymphocytes, including NK cells, converts extracellular ATP (eATP) into AMP and, thus, potentially suppresses eATP-mediated

    更新日期:2020-03-02
  • Matrix-Targeting Immunotherapy Controls Tumor Growth and Spread by Switching Macrophage Phenotype.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-01-15
    Claire Deligne,Devadarssen Murdamoothoo,Anís N Gammage,Martha Gschwandtner,William Erne,Thomas Loustau,Anna M Marzeda,Raphael Carapito,Nicodème Paul,Inés Velazquez-Quesada,Imogen Mazzier,Zhen Sun,Gertraud Orend,Kim S Midwood

    The interplay between cancer cells and immune cells is a key determinant of tumor survival. Here, we uncovered how tumors exploit the immunomodulatory properties of the extracellular matrix to create a microenvironment that enables their escape from immune surveillance. Using orthotopic grafting of mammary tumor cells in immunocompetent mice and autochthonous models of breast cancer, we discovered

    更新日期:2020-03-02
  • Lactic Acidosis Together with GM-CSF and M-CSF Induces Human Macrophages toward an Inflammatory Protumor Phenotype.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-01-10
    Léa Paolini,Clément Adam,Céline Beauvillain,Laurence Preisser,Simon Blanchard,Pascale Pignon,Valérie Seegers,Louise-Marie Chevalier,Mario Campone,Romuald Wernert,Véronique Verrielle,Pedro Raro,Norbert Ifrah,Vincent Lavoué,Philippe Descamps,Alain Morel,Véronique Catros,Guillaume Tcherkez,Guy Lenaers,Cinzia Bocca,Judith Kouassi Nzoughet,Vincent Procaccio,Yves Delneste,Pascale Jeannin

    In established tumors, tumor-associated macrophages (TAM) orchestrate nonresolving cancer-related inflammation and produce mediators favoring tumor growth, metastasis, and angiogenesis. However, the factors conferring inflammatory and protumor properties on human macrophages remain largely unknown. Most solid tumors have high lactate content. We therefore analyzed the impact of lactate on human monocyte

    更新日期:2020-03-02
  • High-Throughput Prediction of MHC Class I and II Neoantigens with MHCnuggets.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2019-12-23
    Xiaoshan M Shao,Rohit Bhattacharya,Justin Huang,I K Ashok Sivakumar,Collin Tokheim,Lily Zheng,Dylan Hirsch,Benjamin Kaminow,Ashton Omdahl,Maria Bonsack,Angelika B Riemer,Victor E Velculescu,Valsamo Anagnostou,Kymberleigh A Pagel,Rachel Karchin

    Computational prediction of binding between neoantigen peptides and major histocompatibility complex (MHC) proteins can be used to predict patient response to cancer immunotherapy. Current neoantigen predictors focus on in silico estimation of MHC binding affinity and are limited by low predictive value for actual peptide presentation, inadequate support for rare MHC alleles, and poor scalability to

    更新日期:2020-03-02
  • pVACtools: A Computational Toolkit to Identify and Visualize Cancer Neoantigens.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-01-06
    Jasreet Hundal,Susanna Kiwala,Joshua McMichael,Christopher A Miller,Huiming Xia,Alexander T Wollam,Connor J Liu,Sidi Zhao,Yang-Yang Feng,Aaron P Graubert,Amber Z Wollam,Jonas Neichin,Megan Neveau,Jason Walker,William E Gillanders,Elaine R Mardis,Obi L Griffith,Malachi Griffith

    Identification of neoantigens is a critical step in predicting response to checkpoint blockade therapy and design of personalized cancer vaccines. This is a cross-disciplinary challenge, involving genomics, proteomics, immunology, and computational approaches. We have built a computational framework called pVACtools that, when paired with a well-established genomics pipeline, produces an end-to-end

    更新日期:2020-03-02
  • RIPK3 orchestrates fatty acid metabolism in tumor-associated macrophages and hepatocarcinogenesis.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-03-02
    Lei Wu,Xiao Zhang,Lu Zheng,Huakan Zhao,Guifang Yan,Qi Zhang,Yu Zhou,Juan Lei,Jiangang Zhang,Jingchun Wang,Rong Xin,Lu Jiang,Jin Peng,Qian Chen,Sin Man Lam,Guanghou Shui,Hongming Miao,Yongsheng Li

    Metabolic reprogramming is critical for the polarization and function of tumor associated macrophages (TAMs) and hepatocarcinogenesis, but how this reprogramming occurs is unknown. Here, we showed that receptor-interacting protein kinase 3 (RIPK3), a central factor in necroptosis, is downregulated in hepatocellular carcinoma (HCC)-associated macrophages, which correlated with tumorigenesis and enhanced

    更新日期:2020-03-02
  • A Sampling of Highlights from the Literature
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-02-01
    American Association for Cancer Research

    ![][1] [ Perfecting CAR therapy (from Oreca 07-Gibson via motors.all-free-photos.com) ][2] Multiple mechanisms thwart the efficacy of CAR T cells. Lynn et al. overexpress the activating c-Jun AP1 complex in various CAR T cells, yielding resistance to exhaustion and strong antitumor

    更新日期:2020-02-03
  • Macrophages Instruct Aberrant Glycosylation in Colon Cancer by Chemokine and Cytokine Signals.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-02-01
    Vincenzo Bronte

    Myeloid cells can alter diverse molecular and metabolic pathways in cancer cells, contributing to their survival, migration, and resistance to chemotherapy and immune attack. The results by Kvorjak and colleagues unveil a novel circuit whereby altered glycosylation in epithelial cells promotes the pathogenesis of ulcerative colitis and colitis-associated colon cancer, via the production of IL13 and

    更新日期:2020-02-03
  • Immunotherapy of Pediatric Solid Tumors: Treatments at a Crossroads, with an Emphasis on Antibodies
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-02-01
    Dana L. Casey; Nai-Kong V. Cheung

    Over the last decade, immunotherapy has rapidly changed the therapeutic landscape and prognosis for many hematologic malignancies and adult solid tumors. Despite this success, immunotherapy for pediatric solid tumors remains in the early stages of development, and significant clinical benefit has yet to be realized, with anti-GD2 for neuroblastoma being the exception. The limited neoepitope expression

    更新日期:2020-02-03
  • Cross-talk between Colon Cells and Macrophages Increases ST6GALNAC1 and MUC1-sTn Expression in Ulcerative Colitis and Colitis-Associated Colon Cancer.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2019-12-12
    Michael Kvorjak,Yasmine Ahmed,Michelle L Miller,Raahul Sriram,Claudia Coronnello,Jana G Hashash,Douglas J Hartman,Cheryl A Telmer,Natasa Miskov-Zivanov,Olivera J Finn,Sandra Cascio

    Patients with ulcerative colitis have an increased risk of developing colitis-associated colon cancer (CACC). Changes in glycosylation of the oncoprotein MUC1 commonly occur in chronic inflammation, including ulcerative colitis, and this abnormally glycosylated MUC1 promotes cancer development and progression. It is not known what causes changes in glycosylation of MUC1. Gene expression profiling of

    更新日期:2020-02-03
  • Targeting CMTM6 Suppresses Stem Cell-Like Properties and Enhances Antitumor Immunity in Head and Neck Squamous Cell Carcinoma.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2019-11-26
    Lei Chen,Qi-Chao Yang,Yi-Cun Li,Lei-Lei Yang,Jian-Feng Liu,Hao Li,Yao Xiao,Lin-Lin Bu,Wen-Feng Zhang,Zhi-Jun Sun

    CMTM6, a regulator of PD-L1 expression, also modulates tumor immunity. Little is known about the function of CMTM6 and its mechanism of action in head and neck squamous cell carcinoma (HNSCC). In this study, we found by IHC analysis that CMTM6 overexpression predicted a poor prognosis for patients with HNSCC. We discovered that CMTM6 expression was correlated with increased activity through the Wnt/β-catenin

    更新日期:2020-02-03
  • Impact of TCR Diversity on the Development of Transplanted or Chemically Induced Tumors.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2019-12-12
    Karin Schreiber,Theodore G Karrison,Steven P Wolf,Kazuma Kiyotani,Madeline Steiner,Eric R Littmann,Eric G Pamer,Thomas Kammertoens,Hans Schreiber,Matthias Leisegang

    Burnet postulated that the diversity of T-cell receptors (TCR) allows T cells to protect against the development of cancers that display antigens with a similar, seemingly endless diversity. To test this hypothesis, we developed a strategy in which a single breeding pair of mice gives rise to four groups of sibling mice. Three of the four groups had a similar number of CD8+ T cells, but TCR diversity

    更新日期:2020-02-03
  • Self-Maintaining CD103+ Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2020-02-01
    Megat Abd Hamid; Huw Colin-York; Nasullah Khalid-Alham; Molly Browne; Lucia Cerundolo; Ji-Li Chen; Xuan Yao; Samara Rosendo-Machado; Craig Waugh; David Maldonado-Perez; Emma Bowes; Clare Verrill; Vincenzo Cerundolo; Christopher P. Conlon; Marco Fritzsche; Yanchun Peng; Tao Dong

    Enrichment of CD103+ tumor-infiltrating T lymphocytes (TIL) is associated with improved outcomes in patients. However, the characteristics of human CD103+ cytotoxic CD8+ T cells (CTL) and their role in tumor control remain unclear. We investigated the features and antitumor mechanisms of CD103+ CTLs by assessing T-cell receptor (TCR)–matched CD103+ and CD103− cancer-specific CTL immunity in vitro and

    更新日期:2020-02-03
  • Aggressive Mammary Cancers Lacking Lymphocytic Infiltration Arise in Irradiated Mice and Can Be Prevented by Dietary Intervention.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2019-12-12
    Coral Omene,Lin Ma,Jade Moore,Haoxu Ouyang,Irineu Illa-Bochaca,William Chou,Manan S Patel,Christopher Sebastiano,Sandra Demaria,Jian-Hua Mao,Kubra Karagoz,Michael L Gatza,Mary Helen Barcellos-Hoff

    Because the incidence of breast cancer increases decades after ionizing radiation exposure, aging has been implicated in the evolution of the tumor microenvironment and tumor progression. Here, we investigated radiation-induced carcinogenesis using a model in which the mammary glands of 10-month-old BALB/c mice were transplanted with Trp53-null mammary tissue 3 days after exposure to low doses of sparsely

    更新日期:2020-02-03
  • CD40 Enhances Type I Interferon Responses Downstream of CD47 Blockade, Bridging Innate and Adaptive Immunity.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2019-12-18
    Suresh de Silva,George Fromm,Casey W Shuptrine,Kellsey Johannes,Arpita Patel,Kyung Jin Yoo,Kaiwen Huang,Taylor H Schreiber

    Disrupting the binding of CD47 to SIRPα has emerged as a promising immunotherapeutic strategy for advanced cancers by potentiating antibody-dependent cellular phagocytosis (ADCP) of targeted antibodies. Preclinically, CD47/SIRPα blockade induces antitumor activity by increasing the phagocytosis of tumor cells by macrophages and enhancing the cross-presentation of tumor antigens to CD8+ T cells by dendritic

    更新日期:2020-02-03
  • Intratumoral Plasmid IL12 Electroporation Therapy in Patients with Advanced Melanoma Induces Systemic and Intratumoral T-cell Responses.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2019-12-18
    Samantha K Greaney,Alain P Algazi,Katy K Tsai,Kathryn T Takamura,Lawrence Chen,Christopher G Twitty,Li Zhang,Alan Paciorek,Robert H Pierce,Mai H Le,Adil I Daud,Lawrence Fong

    Whereas systemic IL12 is associated with potentially life-threatening toxicity, intratumoral delivery of IL12 through tavokinogene telseplasmid electroporation (tavo) is safe and can induce tumor regression at distant sites. The mechanism by which these responses are mediated is unknown but is presumed to result from a cellular immune response. In a phase II clinical trial of tavo (NCT01502293), samples

    更新日期:2020-02-03
  • MicroRNAs in Tumor Exosomes Drive Immune Escape in Melanoma.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2019-12-19
    Virginie Vignard,Maureen Labbé,Nadège Marec,Gwennan André-Grégoire,Nicolas Jouand,Jean-François Fonteneau,Nathalie Labarrière,Delphine Fradin

    MicroRNAs (miRNA), small noncoding RNAs that regulate gene expression, exist not only in cells but also in a variety of body fluids. These circulating miRNAs could enable intercellular communication. miRNAs are packaged in membrane-encapsulated vesicles, such as exosomes, or protected by RNA-binding proteins. Here, we report that miRNAs included in human melanoma exosomes regulate the tumor immune

    更新日期:2020-02-03
  • Immunoregulation and Clinical Implications of ANGPT2/TIE2+ M-MDSC Signature in Non-Small Cell Lung Cancer.
    Cancer Immunol. Res. (IF 8.619) Pub Date : 2019-12-23
    Elodie Lauret Marie Joseph,Caroline Laheurte,Marine Jary,Laura Boullerot,Kamal Asgarov,Eléonore Gravelin,Adeline Bouard,Laurie Rangan,Magalie Dosset,Christophe Borg,Olivier Adotévi

    Myeloid-derived suppressor cells (MDSC) promote immunosuppression and are a target in the field of immuno-oncology. Accumulation of MDSCs is associated with poor prognosis and resistance to immunotherapy for several cancers. Here, we describe an accumulation of a subset of circulating monocytic MDSCs (M-MDSC) overexpressing TIE2, the receptor for angiopoietin-2 (ANGPT2), in patients with non-small

    更新日期:2020-02-03
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