Article
Multidisciplinary Sciences
Antonius A. de Waard, Tamara Verkerk, Kelly Hoefakker, Dirk M. van der Steen, Marlieke L. M. Jongsma, Dganit Melamed Kadosh, Sophie Bliss, Arnoud H. de Ru, Arie Admon, Peter A. van Veelen, Marieke Griffioen, Mirjam H. M. Heemskerk, Robbert M. Spaapen
Summary: The absence of clinically relevant antigens on healthy cells needs to be extensively tested in order to define safe targets for T cell-based immunotherapy.
Article
Multidisciplinary Sciences
Cristina Puig-Saus, Barbara Sennino, Songming Peng, Clifford L. Wang, Zheng Pan, Benjamin Yuen, Bhamini Purandare, Duo An, Boi B. Quach, Diana Nguyen, Huiming Xia, Sameeha Jilani, Kevin Shao, Claire McHugh, John Greer, Phillip Peabody, Saparya Nayak, Jonathan Hoover, Sara Said, Kyle Jacoby, Olivier Dalmas, Susan P. Foy, Andrew Conroy, Michael C. Yi, Christine Shieh, William Lu, Katharine Heeringa, Yan Ma, Shahab Chizari, Melissa J. Pilling, Marc Ting, Ramya Tunuguntla, Salemiz Sandoval, Robert Moot, Theresa Hunter, Sidi Zhao, Justin D. Saco, Ivan Perez-Garcilazo, Egmidio Medina, Agustin Vega-Crespo, Ignacio Baselga-Carretero, Gabriel Abril-Rodriguez, Grace Cherry, Deborah J. Wong, Jasreet Hundal, Bartosz Chmielowski, Daniel E. Speiser, Michael T. Bethune, Xiaoyan R. Bao, Alena Gros, Obi L. Griffith, Malachi Griffith, James R. Heath, Alex Franzusoff, Stefanie J. Mandl, Antoni Ribas
Summary: We isolated neoantigen-specific T cells from blood and tumors of melanoma patients using newly developed technologies. Multiple T cell clones with different neoTCR sequences recognized a limited number of mutations in samples from patients with clinical responses. These recurring neoTCR clonotypes were detected in blood and tumors over time. Patients with no response also showed neoantigen-specific T cell responses, but with lower TCR polyclonality and were not recurrently detected in sequential samples. Reconstructing neoTCRs in donor T cells demonstrated specific recognition and cytotoxicity to patient-matched melanoma cell lines.
Article
Immunology
Andreas Walker, Tatjana Schwarz, Janine Brinkmann-Paulukat, Karin Wisskirchen, Christopher Menne, Elahe Salimi Alizei, Helenie Kefalakes, Martin Theissen, Daniel Hoffmann, Julian Schulze zur Wiesch, Mala K. K. Maini, Markus Cornberg, Anke R. M. Kraft, Verena Keitel, Hans H. H. Bock, Peter A. A. Horn, Robert Thimme, Heiner Wedemeyer, Falko M. M. Heinemann, Tom Luedde, Christoph Neumann-Haefelin, Ulrike Protzer, Joerg Timm
Summary: This study performed a high-resolution analysis of the core(18-27) specific CD8+ T cell and the selected escape pathways in patients with chronic HBV infection. The results demonstrate the promiscuous presentation of the core(18-27) epitope and the selection pressure on the epitope in the context of different HLA class I molecules. Some epitope variants showed evidence for impaired antigen processing and reduced presentation. These findings suggest the importance of considering epitope variants in T cell-based therapy strategies for chronic HBV infection.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Arnaud John Kombe Kombe, Fleury Augustin Nsole Biteghe, Zelia Nelly Ndoutoume, Tengchuan Jin
Summary: Despite the effectiveness of antiviral drug repositioning, convalescent plasma, and current vaccines against SARS-CoV-2, the ongoing emergence of new variants of concern (VOCs) poses challenges in the global COVID-19 pandemic. These VOCs are characterized by mutations that enhance infectivity, evade immune responses, and have significant fatality rates.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Elena Shklovskaya, Helen Rizos
Summary: It is well acknowledged that the immune system plays a role in controlling tumor growth, but tumors can escape immune surveillance through mechanisms like downregulation or loss of MHC-I molecules. This review examines the dysregulation of MHC-I expression in cancer, the nature of MHC-I-bound antigenic peptides, and discusses therapeutic strategies to address MHC-I deficiency in solid tumors with a focus on NK cells and CD4 T cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Yatong Chen, Jing Xu, Xiaodong Wu, Hui Yao, Zhou Yan, Ting Guo, Wenjing Wang, Peixiao Wang, Yu Li, Xiangmin Yang, Hao Li, Huijie Bian, Zhi-Nan Chen
Summary: Deletion of CD147 in T cells limits tumor growth in mouse melanoma and lung cancer. CD147 is upregulated in CD8(+) TILs and coexpressed with immune-checkpoint molecules, leading to increased antitumor responses and potential as a target for cancer immunotherapy.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Oncology
Sabaria Shah, Katherine W. Cook, Peter Symonds, Juliane Weisser, Anne Skinner, Abdullah Al Omari, Samantha J. Paston, Ian Pike, Lindy G. Durrant, Victoria A. Brentville
Summary: This study discovers that homocitrullinated peptides can be processed and presented via MHC-I for tumor therapy. The modified peptides show enhanced binding to HLA-A2 and induce high avidity homocitrulline-specific CD8 T-cell responses, which can kill target cells expressing the peptide.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Renato B. Baleeiro, Christian J. Bouwens, Peng Liu, Carmela Di Gioia, Louisa S. Chard Dunmall, Ai Nagano, Rathistevy Gangeswaran, Claude Chelala, Hemant M. Kocher, Nicholas R. Lemoine, Yaohe Wang
Summary: The expression of MHC II on PDAC cells contributes to the cytotoxicity of CD4+ and CD8+ T-cells against these cells. Stimulation of CD4+ T-cells with neo-antigens can lead to recognition and killing of PDAC cells expressing mutated genes. Combination treatment with IFN-gamma and/or MEK/HDAC inhibitors can induce tumoral MHC II expression on MHC II-negative tumors that are resistant to IFN-gamma. Harnessing MHC II expression on PDAC cells for neo-antigen-based immunotherapy shows potential.
Article
Immunology
Xiaoguang Wang, Brittany C. Waschke, Rachel A. Woolaver, Samantha M. Y. Chen, Zhangguo Chen, Jing H. Wang
Summary: Chemotherapy-treated cancer cells can activate CD8 T cells in an MHC class I-independent manner, leading to the generation of virtual memory (VM) CD8 T cells which may provide superior therapeutic effects on MHC class I-deficient tumors.
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Article
Immunology
Marlieke L. M. Jongsma, Antonius A. de Waard, Matthijs Raaben, Tao Zhang, Birol Cabukusta, Rene Platzer, Vincent A. Blomen, Anastasia Xagara, Tamara Verkerk, Sophie Bliss, Xiangrui Kong, Carolin Gerke, Lennert Janssen, Elmer Stickel, Stephanie Holst, Rosina Plomp, Arend Mulder, Soldano Ferrone, Frans H. J. Claas, Mirjam H. M. Heemskerk, Marieke Griffioen, Anne Halenius, Hermen Overkleeft, Johannes B. Huppa, Manfred Wuhrer, Thijn R. Brummelkamp, Jacques Neefjes, Robbert M. Spaapen
Summary: HLA class I glycoproteins play a crucial role in driving immune responses by presenting antigens, but tumors and pathogens often exploit this process for immune evasion. Through genome-wide screens, it was discovered that the cell surface glycosphingolipid repertoire determines effective HLA-I antigen presentation. Inhibition of GSL synthesis may represent a potential therapeutic target in cancer, infection, and autoimmunity, offering a promising avenue for immune modulation.
Article
Oncology
Katarina Pinjusic, Olivier Andreas Dubey, Olga Egorova, Sina Nassiri, Etienne Meylan, Julien Faget, Daniel Beat Constam
Summary: This study reveals that Activin-A secretion by melanoma cells inhibits adaptive antitumor immunity by indirectly inhibiting CD8(+) T cell infiltration, regardless of BRAF status. It is also found that Activin-A/INHBA expression is correlated with resistance to anti-PD1 therapy in melanoma patients and impairs response to combination anti-cytotoxic T-Lymphocyte associated protein 4/anti-PD1 treatment in preclinical models.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Anna Luise Bernhardt, Julia Zeun, Miriam Marecek, Hannah Reimann, Sascha Kretschmann, Judith Bausenwein, Edith D. van der Meijden, Margarete M. Karg, Tabea Haug, Lisa Meintker, Gloria Lutzny-Geier, Andreas Mackensen, Anita N. Kremer
Summary: The study successfully generated DM-sensitive and DM-resistant variants for two model antigens, demonstrating that DM-sensitive antigens are not inferior to their DM-resistant counterparts in terms of immunogenicity, and can potentially serve as interesting tools for immunotherapy after allogeneic stem cell transplantation.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Weiyu Ge, Ming Yue, Ruirong Lin, Tianhao Zhou, Haiyan Xu, Yu Wang, Tiebo Mao, Shumin Li, Xiuqi Wu, Xiaofei Zhang, Yongchao Wang, Jingyu Ma, Yanling Wang, Shengbai Xue, Daiyuan Shentu, Jiujie Cui, Liwei Wang
Summary: Our study identified a novel metabolic cancer associated fibroblasts subset (meCAFs) enriched in pancreatic ductal adenocarcinoma (PDAC) and related to CD8+ T cells accumulation. The abundance of meCAFs was associated with poor prognosis but better immunotherapy responses in PDAC patients. We demonstrated that PLA2G2A+ meCAFs impede the antitumor immune function of CD8+ T cells and facilitate tumor immune escape in PDAC.
Article
Oncology
Marco Stringhini, Ilaria Spadafora, Marco Catalano, Jacqueline Mock, Philipp Probst, Roman Sporri, Dario Neri
Summary: The study suggests that T cells with single antigen specificity may not be sufficient for effective tumor therapy. In an experiment using autologous T cells targeting a retroviral peptide, the T cells were able to kill tumor cells and inhibit tumor growth in vitro, but failed to induce complete tumor regression in mice, possibly due to the limited survival of injected T cells in vivo. This indicates that future therapeutic strategies using autologous T cells may need to enhance tumor-homing and survival properties of cancer-specific T cells.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Review
Biochemistry & Molecular Biology
Xiaoxu Li, Yinlin Guo, Minmin Xiao, Wenling Zhang
Summary: Tumor cells are capable of evading immune system surveillance, favoring tumor invasion, metastasis, treatment resistance, and recurrence. Epstein-Barr virus (EBV) infection in nasopharyngeal carcinoma (NPC) contributes to a suppressive tumor microenvironment (TME), characterized by the co-existence of EBV-infected NPC cells and tumor-infiltrating lymphocytes. Understanding the interaction between EBV and NPC host cells and the immune escape mechanisms in the TME could lead to the identification of specific immunotherapy targets and the development of effective immunotherapy drugs.
Article
Oncology
Jan Kroon, Martin Puhr, Jeroen T. Buijs, Geertje van der Horst, Danielle M. Hemmer, Koen A. Marijt, Ming S. Hwang, Motasim Masood, Stefan Grimm, Gert Storm, Josbert M. Metselaar, Onno C. Meijer, Zoran Culig, Gabri van der Pluijm
ENDOCRINE-RELATED CANCER
(2016)
Meeting Abstract
Oncology
Zohreh Amoozgar, Teresa E. Peterson, Nathaniel D. Kirkpatrick, Yuhui Huang, Christian T. Farrar, Koen A. Marijt, Jonas Kloepper, Meenal Datta, Giorgio Seano, Keehoon Jung, Walid S. Kamoun, Trupti Vardam, Matija Snuderl, Jermaine Goveia, Sampurna Chatterjee, Ana Batista, Alona Muzikansky, Ching Ching Leow, Lei Xu, Tracy T. Batchelor, Dan G. Duda, Dai Fukumura, Jain K. Jain
Article
Multidisciplinary Sciences
Teresa E. Peterson, Nathaniel D. Kirkpatrick, Yuhui Huang, Christian T. Farrar, Koen A. Marijt, Jonas Kloepper, Meenal Datta, Zohreh Amoozgar, Giorgio Seano, Keehoon Jung, Walid S. Kamoun, Trupti Vardam, Matija Snuderl, Jermaine Goveia, Sampurna Chatterjee, Ana Batista, Alona Muzikansky, Ching Ching Leow, Lei Xu, Tracy T. Batchelor, Dan G. Duda, Dai Fukumura, Rakesh K. Jain
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2016)
Article
Oncology
Elien M. Doorduijn, Marjolein Sluijter, Koen A. Marijt, Bianca J. Querido, Sjoerd H. van der Burg, Thorbald van Hall
Article
Oncology
Jan Willem Kleinovink, Koen A. Marijt, Mark J. A. Schoonderwoerd, Thorbald van Hall, Ferry Ossendorp, Marieke F. Fransen
Article
Immunology
Koen A. Marijt, Laura Blijleven, Els M. E. Verdegaal, Michel G. Kester, Daniel J. Kowalewski, Hans-Georg Rammensee, Stefan Stevanovic, Mirjam H. M. Heemskerk, Sjoerd H. van der Burg, Thorbald van Hall
JOURNAL OF EXPERIMENTAL MEDICINE
(2018)
Article
Oncology
Koen A. Marijt, Marjolein Sluijter, Laura Blijleven, Sofie H. Tolmeijer, Ferenc A. Scheeren, Sjoerd H. van der Burg, Thorbald van Hall
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2019)
Article
Multidisciplinary Sciences
Greta Garrido, Brett Schrand, Ailem Rabasa, Agata Levay, Francesca D'Eramo, Alexey Berezhnoy, Shrey Modi, Tal Gefen, Koen Marijt, Elien Doorduijn, Vikas Dudeja, Thorbald van Hall, Eli Gilboa
NATURE COMMUNICATIONS
(2019)
Article
Oncology
Greta Garrido, Brett Schrand, Agata Levay, Ailem Rabasa, Anthony Ferrantella, Diane M. Da Silva, Francesca D'Eramo, Koen A. Marijt, Zhuoran Zhang, Deukwoo Kwon, Marcin Kortylewski, W. Martin Kast, Vikas Dudeja, Thorbald Van Hall, Eli Gilboa
CANCER IMMUNOLOGY RESEARCH
(2020)
Review
Immunology
Koen A. Marijt, Thorbald van Hall
CURRENT OPINION IN IMMUNOLOGY
(2020)