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mTOR signaling promotes rapid m6A mRNA methylation to regulate NK-cell activation and effector functions Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-04-19 Meng Meng, Zhaoyang Zhong, Liang Song, Zhaohui Zhang, Xiaofeng Yin, Xiqiang Xie, Lei Tian, Wei Wu, Yao Yang, Yafei Deng, Hongyan Peng, Shuting Wu, Guanghe Ran, Yuqing Lin, Qiangqiang Lai, Qinghua Bi, Fulin Yan, Yan Ji, Yang Wang, Xiaohui Li, Ping Yi, Jianhua Yu, Youcai Deng
Natural killer (NK) cells can be rapidly activated in response to cytokines during host defense against malignant cells or viral infection. However, it remains unclear what mechanisms precisely and rapidly regulate the expression of the numerous genes involved in activating NK cells. In this study, we discovered that NK-cell N6-methyladenosine (m6A) methylation levels were rapidly upregulated upon
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SIRT3 negatively regulates TFH cell differentiation in cancer Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-04-17 Yueru Hou, Yejin Cao, Ying He, Lin Dong, Longhao Zhao, Yingjie Dong, Ruiying Niu, Yujing Bi, Guangwei Liu
Follicular helper T (TFH) cells are essential for inducing germinal center (GC) reactions to mediate humoral adaptive immunity in tumors, but the mechanisms underlying TFH cell differentiation remain unclear. Here, we found that the metabolism sensor sirtuin 3 (SIRT3) is critical for TFH cell differentiation and GC formation during tumor and viral infection. SIRT3 deficiency in CD4+ T cells intrinsically
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Orchestrated codelivery of peptide antigen and adjuvant to antigen-presenting cells by using an engineered chimeric peptide enhances antitumor T-cell immunity Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-04-17 Haifeng Pan, Siyuan Yu, Haoyun Zhuang, Han Yang, Jinlu Jiang, Haihui Yang, Shuling Ren, Guoxing Luo, Xuan Yu, Shuping Chen, Yanhua Lin, Roufang Sheng, Shiyin Zhang, Quan Yuan, Chenghao Huang, Tianying Zhang, Tingdong Li, Shengxiang Ge, Jun Zhang, Ningshao Xia
The intrinsic pharmacokinetic limitations of traditional peptide-based cancer vaccines hamper effective cross-presentation and codelivery of antigens and adjuvants, which are crucial for inducing robust antitumor CD8+ T-cell responses. Here, we report the development of a versatile strategy that simultaneously addresses the different pharmacokinetic challenges of soluble subunit vaccines composed of
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Melanoma clonal heterogeneity leads to secondary resistance after adoptive cell therapy with tumor-infiltrating lymphocytes Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-04-17 David König, Michael Sandholzer, Sarp Uzun, Andreas Zingg, Reto Ritschard, Helen Thut, Katharina Glatz, Elisabeth A. Kappos, Dirk J. Schaefer, Christoph Kettelhack, Jakob R. Passweg, Andreas Holbro, Katharina Baur, Michael Medinger, Andreas Buser, Didier Lardinois, Lukas T. Jeker, Nina Khanna, Frank Stenner, Benjamin Kasenda, Krisztian Homicsko, Matthias Matter, Natalia Rodrigues Mantuano, Alfred Zippelius
Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is effective in melanoma patients, although long-term responses seem restricted to patients who have complete remissions. Many patients develop secondary resistance to TIL-ACT but the involved mechanisms are unclear. Here, we describe a case of secondary resistance to TIL-ACT likely due to intratumoral heterogeneity and selection
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Unleashing Natural IL18 Activity Using an Anti-IL18BP Blocker Induces Potent Immune Stimulation and Antitumor Effects Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-04-09 Assaf Menachem, Zoya Alteber, Gady Cojocaru, Tal Fridman Kfir, Dan Blat, Olga Leiderman, Moran Galperin, Lital Sever, Nadav Cohen, Keren Cohen, Roy Z. Granit, Sandra Vols, Masha Frenkel, Liron Soffer, Karin Meyer, Keren Menachem, Hadas Galon Tilleman, Dina Morein, Itamar Borukhov, Amir Toporik, Michal Perpinial Shahor, Evgeny Tatirovsky, Aviram Mizrachi, Adva Levy-Barda, Eran Sadot, Yulia Strenov,
Recombinant cytokines have limited anticancer efficacy mostly due to a narrow therapeutic window and systemic adverse effects. IL18 is an inflammasome-induced proinflammatory cytokine, which enhances T- and NK-cell activity and stimulates IFNγ production. The activity of IL18 is naturally blocked by a high-affinity endogenous binding protein (IL18BP). IL18BP is induced in the tumor microenvironment
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PVRL2 Suppresses Antitumor Immunity through PVRIG- and TIGIT-independent Pathways Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-04-08 Jiuling Yang, Li Wang, James R. Byrnes, Lisa L. Kirkemo, Hannah Driks, Cassandra D. Belair, Oscar A. Aguilar, Lewis L. Lanier, James A. Wells, Lawrence Fong, Robert Blelloch
Poliovirus receptor-related 2 (PVRL2, also known as nectin-2 or CD112) is believed to act as an immune checkpoint protein in cancer; however, most insight into its role is inferred from studies on its known receptor, poliovirus receptor (PVR)-related immunoglobulin domain protein (PVRIG, also known as CD112R). Here, we study PVRL2 itself. PVRL2 levels were found to be high in tumor cells and tumor-derived
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Preclinical Evaluation of Off-The-Shelf PD-L1+ Human Natural Killer Cells Secreting IL15 to Treat Non-Small Cell Lung Cancer Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-04-04 Ting Lu, Rui Ma, Anthony G. Mansour, Christian Bustillos, Zhiyao Li, Zhenlong Li, Shoubao Ma, Kun-Yu Teng, Hanyu Chen, Jianying Zhang, Miguel A. Villalona-Calero, Michael A. Caligiuri, Jianhua Yu
We described previously a human natural killer (NK) cell population that upregulates PD-L1 expression upon recognizing and reacting to tumor cells or exposure to a combination of IL12, IL18 and IL15. Here, to investigate the safety and efficacy of tumor-reactive and cytokine-activated (TRACK) NK cells, human NK cells from umbilical cord blood were expanded, transduced with a retroviral vector encoding
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The neo-open reading frame peptides that comprise the tumor framome are a rich source of neoantigens for cancer immunotherapy Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-04-04 Michael V. Martin, Salvador Aguilar-Rosas, Katka Franke, Mark Pieterse, Jamie van Langelaar, Renee RCE. Schreurs, Maarten F. Bijlsma, Marc G. Besselink, Jan Koster, Wim Timens, Mustafa Khasraw, David M. Ashley, Stephen T. Keir, Christian H. Ottensmeier, Emma V. King, Joanne Verheij, Cynthia Waasdorp, Peter J.M. Valk, Sem AG. Engels, Ellen Oostenbach, Jip T. van Dinter, Damon A. Hofman, Juk Yee Mok
Identification of immunogenic cancer neoantigens as targets for therapy is challenging. Here, we integrate cancer whole genome and long-read transcript sequencing to identify the collection of novel open reading frame peptides (NOPs) expressed in tumors, termed the framome. NOPs represent tumor-specific peptides that are different from wild-type proteins and may be strongly immunogenic. We describe
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Small extracellular vesicle piR-hsa-30937 derived from pancreatic neuroendocrine neoplasms upregulates CD276 in macrophages to promote immune evasion Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-04-04 Yuan Zhong, Ye Tian, Yan Wang, Jian'an Bai, Qin Long, Lijun Yan, Zhihui Gong, Wei Gao, Qiyun Tang
The role of PIWI-interacting RNAs (piRNAs) in small extracellular vesicles (sEV) derived from pancreatic neuroendocrine neoplasms (PNEN) in the tumor microenvironment (TME) remains unexplored. We used multiplex immunohistochemistry (mIHC) to analyze the expression of CD68, CD276 (B7H3) and CD3 on PNEN. CD276+ tumor-associated macrophages (TAMs) were more abundant in tumor tissues than nontumor tissues
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Stressing the Role of CCL3 in Reversing the Immunosuppressive Microenvironment in Gliomas Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-04-03 Xiaoteng Cui, Chunsheng Kang
Patients with gliomas often experience mental health problems, such as depression and anxiety, that lead to worsening tumor progression and shortened survival. In this issue, Wang and colleagues report a novel mechanism underlying this, finding that chronic stress reduces secretion of the chemokine CCL3, which leads to an immunosuppressive glioma microenvironment. CCL3 administration enhances the infiltration
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Interactions between MDSCs and the Autonomic Nervous System: Opportunities and Challenges in Cancer Neuroscience Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-04-03 Lin-Zhen Shu, Yi-Dan Ding, Jin-Yao Zhang, Rui-Shan He, Li Xiao, Bing-Xing Pan, Huan Deng
Myeloid-derived suppressor cells (MDSC) are a population of heterogeneous immune cells that are involved in precancerous conditions and neoplasms. The autonomic nervous system (ANS), which is composed of the sympathetic nervous system and the parasympathetic nervous system, is an important component of the tumor microenvironment that responds to changes in the internal and external environment mainly
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Allogeneic CAR T Cells: Complex Cellular Therapy Designs Test the Limits of Our Preclinical Models Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-04-02 Paolo F. Caimi, Jan Joseph Melenhorst
All chimeric antigen receptor (CAR) T-cell products currently approved by the FDA are autologous, which poses several challenges for widespread use. In this issue, Degagné and colleagues present their preclinical research on creating off-the-shelf CAR T cells for multiple myeloma. They utilized the CRISPR/Cas12a genome editing platform and gene knock-in techniques to eliminate alloreactivity and decrease
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CD4+ Regulatory T Cells in Human Cancer: Subsets, Origin, and Molecular Regulation Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-04-02 Julian Swatler, Marco De Luca, Ivano Rotella, Veronica Lise, Emilia Maria Cristina Mazza, Enrico Lugli
CD4+CD25hiFOXP3+ regulatory T cells (Treg) play major roles in the maintenance of immune tolerance, prevention of inflammation, and tissue homeostasis and repair. In contrast with these beneficial roles, Tregs are abundant in virtually all tumors and have been mechanistically linked to disease progression, metastases development, and therapy resistance. Tregs are thus recognized as a major target for
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Optimal Neoantigen Cancer Vaccines Target CD8+ and CD4+ T Cells with Multiple Antigens Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-04-02 Craig L. Slingluff
Cancer vaccines targeting mutated neoantigens offer promise for prevention of cancer recurrence and for treatment of established cancers. Questions remain about whether vaccines need to target multiple neoantigens and whether they need to target both CD8+ and CD4+ T cells. In this issue, Garzia and colleagues demonstrate the importance of including multiple antigens to stimulate both CD4+ T cells and
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Living in Syn: T Cell Antigen Identification Based on Synapse Sequencing Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-04-01 Venkata Krishna Kanth Makani, Alok V. Joglekar
The pivotal role of T cell responses has been well studied in both protective and destructive scenarios. T cells recognize peptide epitopes presented on Human Leukocyte Antigens (HLA) through their surface T cell receptors (TCR). Advances in single-cell RNA sequencing have identified millions of TCRs, but only a minuscule fraction of them have known epitopes. Recently, cell-based T cell antigen discovery
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Engineering CD3/CD137 Dual Specificity into a DLL3-Targeted T-Cell Engager Enhances T-Cell Infiltration and Efficacy against Small-Cell Lung Cancer Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-04-01 Hirofumi Mikami, Shu Feng, Yutaka Matsuda, Shinya Ishii, Sotaro Naoi, Yumiko Azuma, Hiroaki Nagano, Kentaro Asanuma, Yoko Kayukawa, Toshiaki Tsunenari, Shogo Kamikawaji, Ryutaro Iwabuchi, Junko Shinozuka, Masaki Yamazaki, Haruka Kuroi, Samantha Shu Wen Ho, Siok Wan Gan, Priyanka Chichili, Chai Ling Pang, Chiew Ying Yeo, Shun Shimizu, Naoka Hironiwa, Yasuko Kinoshita, Yuichiro Shimizu, Akihisa Sakamoto
Small-cell lung cancer (SCLC) is an aggressive cancer for which immune checkpoint inhibitors (ICI) have had only limited success. Bispecific T-cell engagers are promising therapeutic alternatives for ICI-resistant tumors, but not all patients with SCLC are responsive. Herein, to integrate CD137 costimulatory function into a T-cell engager format and thereby augment therapeutic efficacy, we generated
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Randomized Phase II Study Evaluating the Addition of Pembrolizumab to Radium-223 in Metastatic Castration-resistant Prostate Cancer Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-03-29 Atish D. Choudhury, Lucia Kwak, Alexander Cheung, Kathryn M. Allaire, Jaqueline Marquez, David D. Yang, Abhishek Tripathi, Jacqueline M. Kilar, Meredith Flynn, Brianna Maynard, Rebecca Reichel, Amanda F. Pace, Brandon K. Chen, Eliezer M. Van Allen, Kerry Kilbridge, Xiao X. Wei, Bradley A. McGregor, Mark M. Pomerantz, Rupal S. Bhatt, Christopher J. Sweeney, Glenn J. Bubley, Heather A. Jacene, Mary-Ellen
The checkpoint immunotherapeutic pembrolizumab induces responses in a small minority of patients with metastatic castration-resistant prostate cancer (mCRPC). Radium-223 (R223) may increase immunogenicity of bone metastases and increase pembrolizumab (P) activity. In a randomized phase II study, we assessed the effect of R223+P compared with R223 on tumor immune infiltration, safety, and clinical outcomes
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The ω-3 polyunsaturated fatty acid docosahexaenoic acid enhances NK-cell antitumor effector functions Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-03-25 Shuting Wu, Hongyan Peng, Songyang Li, Lanlan Huang, Xiangyu Wang, Yana Li, Yongjie Liu, Peiwen Xiong, Qinglan Yang, Kunpeng Tian, Weiru Wu, Rongxi Pu, Xiulan Lu, Zhenghui Xiao, Jian Yang, Zhaoyang Zhong, Yuan Gao, Yafei Deng, Youcai Deng
ω-3 polyunsaturated fatty acids (PUFAs) are known to directly repress tumour development and progression. In this study, we explored whether docosahexaenoic acid (DHA), a type of ω-3 PUFA, had an immunomodulatory role in promoting tumour growth in immunocompetent mice. The number of natural killer (NK) cells but not the number of T or B cells was decreased by DHA supplementation in various tissues
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An IRF2-Expressing Oncolytic Virus Changes the Susceptibility of Tumor Cells to Antitumor T cells and Promotes Tumor Clearance Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-03-22 Lulu Shao, Rashmi Srivastava, Greg M. Delgoffe, Stephen H. Thorne, Saumendra N. Sarkar
Interferon regulatory factor 1 (IRF1) can promote antitumor immunity. However, we have shown previously that in the tumor cell, IRF1 can promote tumor growth, and IRF1-deficient tumor cells exhibit severely restricted tumor growth in several syngeneic mouse tumor models. Here, we investigate the potential of functionally modulating IRF1 to reduce tumor progression and prolong survival. Using inducible
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The exonuclease TREX1 constitutes an innate immune checkpoint limiting cGAS/STING-mediated antitumor immunity Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-03-15 Junghyun Lim, Ryan Rodriguez, Katherine Williams, John Silva, Alan G. Gutierrez, Paul Tyler, Faezzah Baharom, Tao Sun, Eva Lin, Scott Martin, Brandon D. Kayser, Robert J. Johnston, Ira Mellman, Lélia Delamarre, Nathaniel R. West, Sören Müller, Yan Qu, Klaus Heger
The DNA exonuclease TREX1 (Three-prime repair exonuclease 1) is critical for preventing autoimmunity in mice and humans by degrading endogenous cytosolic DNA, which otherwise triggers activation of the innate cGAS/STING pathway leading to the production of type I IFNs. Since tumor cells are prone to aberrant cytosolic DNA accumulation, we hypothesized that they are critically dependent on TREX1 activity
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Chronic stress exacerbates the immunosuppressive microenvironment and progression of gliomas by reducing secretion of CCL3 Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-03-04 Xu Wang, Long Zhang, Yi Zhou, Yan Wang, Xiang Wang, Yining Zhang, Ankang Quan, Yufei Mao, Yu Zhang, Ji Qi, Zhongyu Ren, Linbo Gu, Rutong Yu, Xiuping Zhou
As understanding of cancer has deepened, increasing attention has been turned to the roles of psychological factors, especially chronic stress–induced depression, in the occurrence and development of tumors. However, whether and how depression affects the progression of gliomas are still unclear. In this study, we have revealed that chronic stress inhibited the recruitment of tumor-associated macrophages
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Intratumoral TREX1 induction promotes immune evasion by limiting type I interferon Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-02-26 Eléonore Toufektchan, Alexandra Dananberg, Josefine Striepen, James H. Hickling, Abraham Shim, Yanyang Chen, Ashley Nichols, Mercedes A. Duran Paez, Lisa Mohr, Samuel F. Bakhoum, John Maciejowski
Chromosomal instability is a hallmark of human cancer that is associated with aggressive disease characteristics. Chromosome mis-segregations help fuel natural selection, but they risk provoking a cGAS-STING immune response through the accumulation of cytosolic DNA. The mechanisms of how tumors benefit from chromosomal instability while mitigating associated risks, such as enhanced immune surveillance
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High dimensional analyses reveal IL-15 enhances activation of Sipuleucel-T lymphocyte subsets and reverses immunoresistance Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-02-26 Muhammad A. Saeed, Bo Peng, Kevin Kim, Kavita Rawat, Lindsey M. Kuehm, Zoe R. Siegel, Ariel Borkowski, Nabih Habib, Brian Van Tine, Nadeem Sheikh, Vu Tuyen, Daniel L.J. Thorek, Todd A. Fehniger, Russell K. Pachynski
Sipuleucel-T (sip-T) is the only FDA-approved autologous cellular immunotherapy for metastatic castration-resistant prostate cancer (mCRPC). To elucidate parameters of the response profile to this therapy, we report high-dimensional analyses of sip-T using cytometry by time of flight (CyTOF) and show a lymphoid predominance, with CD3+ T cells constituting the highest proportion (median ~60%) of sip-T
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The TOPK inhibitor HI-TOPK-032 enhances CAR T-cell therapy of hepatocellular carcinoma by upregulating memory T cells Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-02-26 Qunfang Zhang, Fang Zheng, Yuchao Chen, Chun-Ling Liang, Huazhen Liu, Feifei Qiu, Yunshan Liu, Hongfeng Huang, Weihui Lu, Zhenhua Dai
Chimeric antigen receptor (CAR) T cells are emerging as an effective antitumoral therapy. However, their therapeutic effects on solid tumors are limited due to their short survival time and the immunosuppressive tumor microenvironment. Memory T cells respond more vigorously and persist longer than their naive/effector counterparts. Therefore, promoting CAR T-cell development into memory T cells could
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ILT2 and ILT4 drive myeloid suppression via both overlapping and distinct mechanisms Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-02-23 Jane Tian, Amir M. Ashique, Sabrina Weeks, Tian Lan, Hong Yang, Hung-I H. Chen, Christina Song, Kikuye Koyano, Kalyani Mondal, Daniel Tsai, Isla Cheung, Mehrdad Moshrefi, Avantika Kekatpure, Bin Fan, Betty Li, Samir Qurashi, Lauren Rocha, Jonathan Aguayo, Col Rodgers, Marchelle Meza, Darren Heeke, Sara M. Medfisch, Chun Chu, Shelley Starck, Nandini Pal. Basak, Satish Sankaran, Mohit Malhotra, Suzanne
Solid tumors are dense three-dimensional (3D) multi-cellular structures that enable efficient receptor–ligand trans interactions via close cell–cell contact. Immunoglobulin-like transcript (ILT)2 and ILT4 are related immune suppressive receptors that play a role in the inhibition of myeloid cells within the tumor microenvironment. The relative contributions of ILT2 and ILT4 to immune inhibition in
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ANXA3-rich exosomes derived from tumor-associated macrophages regulate ferroptosis and lymphatic metastasis of laryngeal squamous cell carcinoma Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-02-23 Licheng Xu, Wenjing Li, Danxi Liu, Jing Cao, Jingchun Ge, Xinyu Liu, Yue Wang, Yujian Teng, Pengyan Liu, Xinyue Guo, Chen He, Ming Liu, Linli Tian
Tumor-associated macrophages (TAMs) induce immunosuppression in laryngeal squamous cell carcinoma (LSCC). The interaction between LSCC cells and TAMs affects the progression of laryngeal cancer through exosomes, but the underlying molecular mechanism remains unclear. Proteomics analysis of TAMs isolated from human laryngeal tumor tissues obtained from patients with confirmed lymphatic metastasis revealed
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Machine learning links T-cell function and spatial localization to neoadjuvant immunotherapy and clinical outcome in pancreatic cancer Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-02-21 Katie E. Blise, Shamilene Sivagnanam, Courtney B. Betts, Konjit Betre, Nell Kirchberger, Benjamin J. Tate, Emma E. Furth, Andressa Dias Costa, Jonathan A. Nowak, Brian M. Wolpin, Robert H. Vonderheide, Jeremy Goecks, Lisa M. Coussens, Katelyn T. Byrne
Tumor molecular datasets are becoming increasingly complex, making it nearly impossible for humans alone to effectively analyze them. Here, we demonstrate the power of using machine learning (ML) to analyze a single-cell, spatial, and highly multiplexed proteomic dataset from human pancreatic cancer and reveal underlying biological mechanisms that may contribute to clinical outcome. We designed a multiplex
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Immunomodulatory Effects of RANK/RANKL Blockade in Patients with Cancer Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-02-19 Elham Nasrollahi, Diwakar Davar
In cancer, multiple factors converge upon receptor activator of nuclear factor κB (RANK) and its ligand (RANKL) signaling to promote the development of bone metastases; agents that inhibit RANKL signaling reduce skeletal-related events (SRE) in patients with cancer. In addition, RANKL signaling is important in augmenting the ability of dendritic cells (DC) to stimulate both naïve T-cell proliferation
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Tsyn-seq: a T cell synapse–based antigen identification platform Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-02-16 Yimei Jin, Takahiko Miyama, Alexandria Brown, Tomo Hayase, Xingzhi Song, Anand K. Singh, Licai Huang, Ivonne I. Flores, Lauren K. McDaniel, Israel Glover, Taylor M. Halsey, Rishika Prasad, Valerie Chapa, Saira Ahmed, Jianhua Zhang, Kunal Rai, Christine B. Peterson, Gregory Lizee, Jennifer Karmouch, Eiko Hayase, Jeffrey J. Molldrem, Chia-Chi Chang, Wen-Bin Tsai, Robert R. Jenq
Tools for genome-wide rapid identification of peptide–major histocompatibility complex targets of T-cell receptors (TCRs) are not yet universally available. We present a new antigen screening method, the T-synapse (Tsyn) reporter system, which includes antigen-presenting cells (APCs) with a Fas-inducible NF-κB reporter and T cells with a nuclear factor of activated T cells (NFAT) reporter. To functionally
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Neutrophils mediate protection against colitis and carcinogenesis by controlling bacterial invasion and IL-22 production by γδ T cells Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-02-13 Silvia Carnevale, Andrea Ponzetta, Anna Rigatelli, Roberta Carriero, Simone Puccio, Domenico Supino, Giovanna Grieco, Piera Molisso, Irene Di Ceglie, Francesco Scavello, Chiara Perucchini, Fabio Pasqualini, Camilla Recordati, Claudio Tripodo, Beatrice Belmonte, Andrea Mariancini, Paolo Kunderfranco, Giuseppe Sciumè, Enrico Lugli, Eduardo Bonavita, Elena Magrini, Cecilia Garlanda, Alberto Mantovani
Neutrophils are the most abundant leukocytes in human blood and play a primary role in resistance against invading microorganisms and in the acute inflammatory response. However, their role in colitis and colitis-associated colorectal cancer is still under debate. This study aims to dissect the role of neutrophils in these pathological contexts by using a rigorous genetic approach. Neutrophil-deficient
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High-specificity CRISPR-mediated genome engineering in anti-BCMA allogeneic CAR T cells suppresses allograft rejection in preclinical models Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-02-12 Émilie Degagné, Paul D. Donohoue, Suparna Roy, Jessica Scherer, Tristan W. Fowler, Ryan T. Davis, Gustavo A. Reyes, George Kwong, Morena Stanaway, Vanina Larroca Vicena, Devin Mutha, Raymond Guo, Leslie Edwards, Benjamin Schilling, McKay Shaw, Stephen C. Smith, Bryan Kohrs, Heinrich J. Kufeldt, Glen Churchward, Finey Ruan, David B. Nyer, Kyle McSweeney, Matthew J. Irby, Christopher K. Fuller, Lynda
Allogeneic chimeric antigen receptor (CAR) T-cell therapies hold the potential to overcome many of the challenges associated with patient-derived (autologous) CAR T cells. Key considerations in the development of allogeneic CAR T-cell therapies include prevention of GvHD and suppression of allograft rejection. Here we describe preclinical data supporting the ongoing first-in-human clinical study, the
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Intragenic Rearrangement Burden Associates with Immune Cell Infiltration and Response to Immune Checkpoint Blockade in Cancer Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-02-12 Han Zhang, Sanghoon Lee, Renee R. Muthakana, Binfeng Lu, David N. Boone, Daniel Lee, Xiao-Song Wang
Immune checkpoint blockade (ICB) can induce durable cancer remission. However, only a small subset of patients gains benefits. While tumor mutation burden (TMB) differentiates responders from nonresponders in some cases, it is a weak predictor in tumor types with low mutation rates. Thus, there is an unmet need to discover a new class of genetic aberrations that predict ICB responses in these tumor
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Gut mycobiota dysbiosis is associated with melanoma and response to anti-PD-1 therapy Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-02-05 Natalia Szóstak, Luiza Handschuh, Anna Samelak-Czajka, Katarzyna Tomela, Bernadeta Pietrzak, Marcin Schmidt, Łukasz Galus, Jacek Mackiewicz, Andrzej Mackiewicz, Piotr Kozlowski, Anna Philips
Recent research indicates that gut microbiota may be vital in the advancement of melanoma. In this study we found that melanoma patients exhibited a distinct gut mycobiota structure compared to healthy participants. Candida albicans, Candida dubliniensis, and Neurospora crassa were more abundant in samples from patients with melanoma, while Saccharomyces cerevisiae and Debaryomyces hansenii were less
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NCI Resources for Cancer Immunoprevention Research Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-02-01 Shizuko Sei, Sudhir Srivastava, Halonna R. Kelly, Mark Steven. Miller, Wolfgang W. Leitner, Robert H. Shoemaker, Eva Szabo, Philip E. Castle
Cancer prevention and early detection, the first two of the eight primary goals of the National Cancer Plan released in April 2023, are at the forefront of the nation’s strategic efforts to reduce cancer incidence and mortality. The Division of Cancer Prevention (DCP) of the National Cancer Institute (NCI) is the federal government’s principal component devoted to promoting and supporting innovative
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An NFAT1-C3a-C3aR Positive Feedback Loop in Tumor-Associated Macrophages Promotes a Glioma Stem Cell Malignant Phenotype Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-01-30 Yaochuan Zhang, Yifu Song, Xiaoliang Wang, Mengwu Shi, Yibin Lin, Dongxia Tao, Sheng Han
Extensive infiltration by tumor-associated macrophages (TAM) in combination with myeloid-derived suppressor cells constitute the immunosuppressive microenvironment and promote the malignant phenotype of gliomas. The aggressive mesenchymal (MES)-subtype glioma stem cells (GSC) are prominent in the immunosuppressive microenvironment of gliomas. However, the underlying immune-suppressive mechanisms are
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The immune suppressor IGSF1 as a potential target for cancer immunotherapy Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-01-30 Dong-In Koh, Minki Lee, Yoon Sun Park, Jae-Sik Shin, Joseph Kim, Yea Seong Ryu, Jun Hyung Lee, Seunggeon Bae, Mi So Lee, Jun Ki Hong, Hong Rae Jeong, Mingee Choi, Seung-Woo Hong, Dong Kwan Kim, Hyun-kyung Lee, Bomi Kim, Yoo Sang Yoon, Dong-Hoon Jin
The development of first-generation immune checkpoint inhibitors targeting PD-1/PD-L1 and CTLA-4 ushered in a new era in anticancer therapy. While immune checkpoint blockade therapies have shown clinical success, a significant number of patients yet fail to benefit. According to recent reports, many studies are underway to discover next-generation immunotherapeutic targets. Here, we identified a novel
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Dual chimeric antigen receptor T cells targeting CD38 and SLAMF7 with independent signalling demonstrate preclinical efficacy and safety in Multiple Myeloma Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-01-30 Nathalie Roders, Cecilia Nakid-Cordero, Fabio Raineri, Maxime Fayon, Audrey Abecassis, Caroline Choisy, Elisabeth Nelson, Claire Maillard, David Garrick, Alexis Talbot, Jean-Paul Fermand, Bertrand Arnulf, Jean-Christophe Bories
Chimeric antigen receptor T-cell (CAR-T) therapy for multiple myeloma (MM) targeting B-cell maturation antigen (BCMA) induces high overall response rates. However, relapse still occurs and novel strategies for targeting MM cells using CAR-T are needed. SLAMF7 (also known as CS1) and CD38 on tumour plasma cells represent potential alternative targets for CAR-T in MM, but their expression on activated
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Immune modulation with RANKL blockade through denosumab treatment in patients with cancer Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-01-29 Hewitt Chang, Jaqueline Marquez Garcia, Brandon K. Chen, Daniel M. Kim, Michael L. Cheng, Eric V. Liu, Hai Yang, Li Zhang, Meenal Sinha, Alexander Cheung, Serena S. Kwek, Eric D. Chow, Mark Bridge, Rahul R. Aggarwal, Terence W. Friedlander, Eric J. Small, Mark Anderson, Lawrence Fong
Denosumab is a fully human monoclonal antibody that binds receptor activator of nuclear factor-κB ligand (RANKL). It is routinely administered to cancer patients to reduce the incidence of new bone metastasis. RANK–RANKL interactions regulate bone turnover by controlling osteoclast recruitment, development, and activity. However, these interactions also can regulate immune cells including dendritic
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Lymph Node–Targeted Vaccine Boosting of TCR T-cell Therapy Enhances Antitumor Function and Eradicates Solid Tumors Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-01-25 Dylan J. Drakes, Abdulraouf M. Abbas, Jacqueline Shields, Martin P. Steinbuck, Aniela Jakubowski, Lochana M. Seenappa, Christopher M. Haqq, Peter C. DeMuth
T-cell receptor (TCR)–modified T-cell therapies have shown promise against solid tumors, but overall therapeutic benefits have been modest due in part to suboptimal T-cell persistence and activation in vivo, alongside potential tumor antigen escape. In this study, we demonstrate an approach to enhance the in vivo persistence and function of TCR T cells through combination with Amphiphile (AMP) vaccination
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Reprogramming the Intrahepatic Cholangiocarcinoma Immune Microenvironment by Chemotherapy and CTLA-4 Blockade Enhances Anti-PD1 Therapy Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-01-23 Jiang Chen, Zohreh Amoozgar, Xin Liu, Shuichi Aoki, Zelong Liu, Sarah M. Shin, Aya Matsui, Alexei Hernandez, Zhangya Pu, Stefan Halvorsen, Pin-Ji Lei, Meenal Datta, Lingling Zhu, Zhiping Ruan, Lei Shi, Daniel Staiculescu, Koetsu Inoue, Lance L. Munn, Dai Fukumura, Peigen Huang, Slim Sassi, Nabeel Bardeesy, Won Jin Ho, Rakesh K. Jain, Dan G. Duda
Intrahepatic cholangiocarcinoma (ICC) has limited therapeutic options and a dismal prognosis. Adding blockade of the PD1 pathway to gemcitabine/cisplatin chemotherapy has recently shown efficacy in biliary tract cancers but with low response rates. Here, we studied the effects of anti-CTLA-4 when combined with anti-PD1 and gemcitabine/cisplatin in orthotopic murine models of ICC. This combination therapy
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T cell states, repertoire and function in classical Hodgkin lymphoma revealed through single-cell analyses Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-01-19 Xiufen Chen, Jovian Yu, Girish Venkataraman, Sonali M. Smith, Mengjie Chen, Alan Cooper, Sravya Tumuluru, Joshua D. Brody, James Godfrey, Justin Kline
The classical Hodgkin lymphoma (cHL) environment is comprised of a dense and complex immune cell infiltrate interspersed with rare malignant Hodgkin-Reed-Sternberg (HRS) cells. HRS cells are actively surveilled by endogenous T cells, but data linking phenotypic and functional T cell states with clonality at the single cell level in cHL is lacking. To address this knowledge gap, we performed paired
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Translating Science into Survival: Report on the Seventh International Cancer Immunotherapy Conference Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-01-17 Jan D. Beck, Juliana Kenski, Milena Perrone, Arianna Pocaterra, Karen Honey
From September 20 to 23, 2023, the Seventh International Cancer Immunotherapy Conference was hosted jointly by the Cancer Research Institute, the European Network for Cancer Immunotherapy (ENCI), and the American Association for Cancer Research (AACR) in Milan, Italy. The four-day event covered the latest advances in cancer immunology and immunotherapy.
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Tumor-Derived RAB21+ABHD12+ sEVs Drive the Premetastatic Microenvironment in the Lung Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-01-12 Kun Wu, Yan Li, Yikang Ji, Chun Liu, Xiaoning Wang, Haiyan Guo, Jianjun Zhang, Yue He
Tumor metastasis is a spatial and temporal process that starts with remodeling to generate a proper premetastatic niche in a distant tissue. Infiltration of immunosuppressive macrophages is one of the notable characteristics in the premetastatic niche, which is a fundamental requirement for primary tumor metastasis. Here, we demonstrated that small extracellular vesicles (sEV) carrying RAB21 homed
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Neutralizing antibodies impair the oncolytic efficacy of reovirus but permit effective combination with T cell–based immunotherapies Cancer Immunol. Res. (IF 10.1) Pub Date : 2024-01-09 Christianne Groeneveldt, Priscilla Kinderman, Lisa Griffioen, Olivia Rensing, Camilla Labrie, Diana J M. van den Wollenberg, Rob C. Hoeben, Matthew Coffey, Houra Loghmani, Els M.E. Verdegaal, Marij J.P. Welters, Sjoerd H. van der Burg, Thorbald van Hall, Nadine van Montfoort
Reovirus type 3 Dearing (Reo), manufactured for clinical application as Pelareorep, is an attractive anticancer agent under evaluation in multiple phase 2 clinical trials for the treatment of solid tumors. It elicits its anticancer efficacy by inducing both oncolysis and intratumoral T-cell influx. Since most people have been preexposed to Reo, neutralizing antibodies (NAbs) are prevalent in cancer
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FcγRIIB is an immune checkpoint limiting the activity of Treg-targeting antibodies in the tumor microenvironment Cancer Immunol. Res. (IF 10.1) Pub Date : 2023-12-26 David A. Knorr, Lucas Blanchard, Rom S. Leidner, Shawn M. Jensen, Ryan Meng, Andrew Jones, Carmen Ballesteros-Merino, Richard B. Bell, Maria Baez, Alessandra Marino, David Sprott, Carlo B. Bifulco, Brian Piening, Rony Dahan, Juan C. Osorio, Bernard A. Fox, Jeffrey V. Ravetch
Preclinical murine data indicate that Fc-dependent depletion of intratumoral regulatory T cells (Tregs) is a major mechanism of action of anti–CTLA-4. However, the two main antibodies administered to patients (Ipilimumab and Tremelimumab) do not recapitulate these effects. Here, we investigate the underlying mechanisms responsible for the limited Treg depletion observed with these therapies. Using
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LILRB3 supports immunosuppressive activity of myeloid cells and tumor development Cancer Immunol. Res. (IF 10.1) Pub Date : 2023-12-19 Ryan Huang, Xiaoye Liu, Jaehyup Kim, Hui Deng, Mi Deng, Xun Gui, Heyu Chen, Guojin Wu, Wei Xiong, Jingjing Xie, Cheryl Lewis, Jade Homsi, Xing Yang, Chengcheng Zhang, Yubo He, Qi Lou, Caroline Smith, Samuel John, Ningyan Zhang, Zhiqiang An, Chengcheng Zhang
The existing T cell–centered immune checkpoint blockade therapies have been successful in treating some but not all patients with cancer. Immunosuppressive myeloid cells, including myeloid-derived suppressor cells (MDSCs), that inhibit antitumor immunity and support multiple steps of tumor development are recognized as one of the major obstacles in cancer treatment. Leukocyte Ig-like receptor subfamily
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Immune-related colitis is associated with fecal microbial dysbiosis and can be mitigated by fecal microbiota transplantation Cancer Immunol. Res. (IF 10.1) Pub Date : 2023-12-18 Arielle Elkrief, Nicholas R. Waters, Natalie Smith, Anqi Dai, John Slingerland, Nathan Aleynick, Binita Febles, Pooja Gogia, Nicholas D. Socci, Melissa Lumish, Paul A. Giardina, Jamie E. Chaft, Juliana Eng, Robert J. Motzer, Robin B. Mendelsohn, Kate A. Markey, Mingqiang Zhuang, Yanyun Li, Zhifan Yang, Travis J. Hollmann, Charles M. Rudin, Marcel R.M. van den Brink, Jinru Shia, Susan DeWolf, Adam J
Colitis induced by treatment with immune checkpoint inhibitors (ICI), termed irColitis, is a substantial cause of morbidity complicating cancer treatment. We hypothesized that abnormal fecal microbiome features would be present at the time of irColitis onset, and that restoring the microbiome with fecal transplant from a healthy donor would mitigate disease severity. Herein, we present fecal microbiota
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M9657 is a bispecific tumor-targeted anti-CD137 agonist that induces MSLN-dependent antitumor immunity without liver inflammation Cancer Immunol. Res. (IF 10.1) Pub Date : 2023-12-13 Chunxiao Xu, Xueyuan Zhou, Lindsay Webb, Sireesha Yalavarthi, Wenxin Zheng, Somdutta Saha, Rene Schweickhardt, Maria Soloviev, Molly H. Jenkins, Susanne Brandstetter, Natalya Belousova, Marat Alimzhanov, Brian Rabinovich, Amit M. Deshpande, Neil Brewis, Laura Helming
The costimulatory receptor CD137 (also known as TNFRSF9 or 4-1BB) sustains effective cytotoxic T-cell responses. Agonistic anti-CD137 cancer immunotherapies are being investigated in clinical trials. Development of the first-generation CD137-agonist monotherapies utomilumab and urelumab was unsuccessful due to low antitumor efficacy mediated by the epitope recognized on CD137 or hepatotoxicity mediated
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Single-cell transcriptomics reveals the heterogeneity of the immune landscape of IDH-wildtype high-grade gliomas Cancer Immunol. Res. (IF 10.1) Pub Date : 2023-12-13 Xiaojuan Ran, Jian Zheng, Lingchao Chen, Zhen Xia, Yin Wang, Chengfang Sun, Chen Guo, Peng Lin, Fuyi Liu, Chun Wang, Jianguo Zhou, Chongran Sun, Qichang Liu, Jianzhu Ma, Zhiyong Qin, Xiangdong Zhu, Qi Xie
Isocitrate dehydrogenase (IDH)-wildtype (WT) high-grade gliomas, especially glioblastomas, are highly aggressive and have an immunosuppressive tumor microenvironment. Although tumor-infiltrating immune cells are known to play a critical role in glioma genesis, their heterogeneity and intercellular interactions remain poorly understood. In this study, we constructed a single-cell transcriptome landscape
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Immune modulation of innate and adaptive responses restores immune surveillance and establishes anti-tumor immunological memory Cancer Immunol. Res. (IF 10.1) Pub Date : 2023-12-11 Ayesha B. Alvero, Alexandra Fox, Bhaskara Reddy Madina, Marie M. Krady, Radhika Gogoi, Hussein Chehade, Valerian Nakaar, Bijan Almassian, Timur O. Yarovinsky, Thomas Rutherford, Gil Mor
Current immunotherapies have proven effective in strengthening anti-tumor immune responses, but constant opposing signals from tumor cells and the surrounding microenvironment eventually lead to immune escape. We hypothesized that in situ release of antigens and regulation of both the innate and adaptive arms of the immune system would provide a robust and long-term anti-tumor effect by creating immunological
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Intracellular K+ Limits T-cell Exhaustion and Preserves Antitumor Function Cancer Immunol. Res. (IF 10.1) Pub Date : 2023-12-08 Camille Collier, Kelly Wucherer, Matthew McWhorter, Chelsea Jenkins, Alexandra Bartlett, Rahul Roychoudhuri, Robert Eil
T cells are often compromised within cancers, allowing disease progression. We previously found that intratumoral elevations in extracellular K+, related to ongoing cell death, constrained CD8+ T-cell Akt–mTOR signaling and effector function. To alleviate K+-mediated T-cell dysfunction, we pursued genetic means to lower intracellular K+. CD8+ T cells robustly and dynamically express the Na+/K+ ATPase
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CD8+ T Cells Keep Their (K+)urrency for Function Cancer Immunol. Res. (IF 10.1) Pub Date : 2023-12-08 Alma Banuelos, Henrique Borges da Silva
CD8+ T-cell responses are influenced by ion abundance, which can widely vary within the tumor microenvironment. In this issue, Collier and colleagues investigated how intracellular versus extracellular potassium ion (K+) regulates intratumoral CD8+ T cells. They show that, while excessive extracellular K+ induces exhaustion, intracellular K+ is needed for protection from dysfunction. This work shows
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Innate Lymphoid Cells in Bladder Cancer: From Mechanisms of Action to Immune Therapies Cancer Immunol. Res. (IF 10.1) Pub Date : 2023-12-07 Onika D.V. Noel, Zaineb Hassouneh, Robert S. Svatek, Neelam Mukherjee
Bladder tumors have a high mutational burden and tend to be responsive to immune therapies; however, response rates remain modest. To date, immunotherapy in bladder cancer has largely focused on enhancing T-cell immune responses in the bladder tumor microenvironment. It is anticipated that other immune cells, including innate lymphoid cells (ILC), which play an important role in bladder oncogenesis
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RALDH1 inhibition shows immunotherapeutic efficacy in hepatocellular carcinoma Cancer Immunol. Res. (IF 10.1) Pub Date : 2023-12-05 Pengfei Yu, Shuwen Cao, Shyh-Ming Yang, Ganesha Rai, Natalia J. Martinez, Adam Yasgar, Alexey V. Zakharov, Anton Simeonov, William A. Molina-Arocho, Graham P. Lobel, Hesham Mohei, Alexis L. Scott, Li Zhai, Emma E. Furth, M Celeste. Simon, Malay Haldar
Globally, hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers and a leading cause of cancer-related death. We previously identified an immune evasion pathway whereby tumor cells produce retinoic acid (RA) to promote differentiation of intratumoral monocytes into pro-tumor macrophages. Retinaldehyde dehydrogenase 1 (RALDH1), RALDH2, and RALDH3 are the three isozymes that catalyze
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Engagement of CD99 activates distinct programs in Ewing sarcoma and macrophages Cancer Immunol. Res. (IF 10.1) Pub Date : 2023-12-05 Maria Cristina Manara, Cristina Manferdini, Camilla Cristalli, Marianna Carrabotta, Spartaco Santi, Alessandra De Feo, Giulia Caldoni, Michela Pasello, Lorena Landuzzi, Pier-Luigi Lollini, Francesca Salamanna, Sabrina Dominici, Valentina Fiori, Mauro Magnani, Gina Lisignoli, Katia Scotlandi
Ewing sarcoma (EWS) is the second most common pediatric bone tumor. The EWS tumor microenvironment is largely recognized as immune-cold, with macrophages being the most abundant immune cells and their presence associated with worse patient prognosis. Expression of CD99 is a hallmark of EWS cells, and its targeting induces inhibition of EWS tumor growth through a poorly understood mechanism. In this
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A metabolic axis of immune intractability Cancer Immunol. Res. (IF 10.1) Pub Date : 2023-11-21 Dominique C. Hinshaw, Meet Patel, Lalita A. Shevde
Immune cells in the tumor niche robustly influence disease progression. Remarkably, in cancer, developmental pathways are re-enacted. Many parallels between immune regulation of embryonic development and immune regulation of tumor progression can be drawn, with evidence clearly supporting an immune-suppressive microenvironment in both situations. In these ecosystems, metabolic and bioenergetic circuits
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Separating the Good from the Bad: Tumor-Infiltrating Tregs Have Increased Fucosylation Cancer Immunol. Res. (IF 10.1) Pub Date : 2023-11-15 Stephanie Silveria, Michel DuPage
Regulatory T cells (Treg) can suppress antitumor immune responses, and their presence in tumors is associated with worse prognoses in most cancers. Strategies to neutralize Treg-mediated suppression in tumors without immune-related adverse events, however, are challenging due to the essential role of Tregs in maintaining immune homeostasis. In this issue, Pinioti and colleagues identify fucosylation
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Combination anti-PD-1 and electroacupuncture induces a potent anti-tumor immune response in microsatellite-stable colorectal cancer Cancer Immunol. Res. (IF 10.1) Pub Date : 2023-11-13 Yuan Wang, Fengyi Liu, Xiaoxue Du, Jiaqi Shi, Rui Yu, Shuang Li, Ruisi Na, Ying Zhao, Meng Zhou, Ying Guo, Liang Cheng, Guangyu Wang, Tongsen Zheng
Programmed death receptor-1 (PD-1) inhibitors are ineffective against microsatellite-stable (MSS) colorectal cancer (CRC). Electroacupuncture (EA) has onco-suppressive and immunomodulatory properties. Here, we investigated the anti-tumor effects of EA and explored the feasibility of EA combined with anti-PD-1 in MSS CRC. Results showed that EA exerted its anti-tumor effect in an intensity-specific
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The tautomerase activity of tumor exosomal MIF promotes pancreatic cancer progression by modulating MDSC differentiation Cancer Immunol. Res. (IF 10.1) Pub Date : 2023-11-13 Xuebing Jia, Jianbei Xi, Binle Tian, Yuanyuan Zhang, Zhilong Wang, Fan Wang, Zheng Li, Jiang Long, JianFei Wang, Guo-Huang Fan, Qi Li
Pancreatic cancer is a deadly disease that is largely resistant to immunotherapy, in part because of the accumulation of immunosuppressive cells in the tumor microenvironment (TME). Much evidence suggests that tumor-derived exosomes contribute to the immunosuppressive activity mediated by myeloid-derived suppressor cells (MDSCs) within the pancreatic cancer TME. However, the underlying mechanisms remain
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Battle Within the Sexes: Differences in Male and Female Immunity and the Impact on Antitumor Responses Cancer Immunol. Res. (IF 10.1) Pub Date : 2023-11-08 Katey S. Hunt, Elise Alspach
The immune system plays critical roles in regulating tumor progression. However, despite established differences in male and female immune cell function, our appreciation of sex as a variable in antitumor immune responses is only beginning to develop. Recent findings in mice have demonstrated for the first time that disparities in cancer incidence between the sexes are driven in part by differences