Review
Immunology
Ryuhjin Ahn, Yufei Cui, Forest M. White
Summary: Effective T cell antitumor immunity is essential for successful cancer immunotherapy. Mass spectrometry-based survey of tumor antigens (immunopeptidomics) combined with other omics platforms has contributed to the identification and quantification of T cell antigens. This review discusses the types of tumor antigens for targeted cancer immunotherapy and the importance of immunopeptidomics methods in MHC peptide identification. It also highlights the integration of mass spectrometry-driven approaches with other technologies in the discovery of targetable T cell antigens for cancer immunotherapy.
SEMINARS IN IMMUNOLOGY
(2023)
Article
Oncology
Catherine M. Ade, Matthew J. Sporn, Sudipto Das, Zhiya Yu, Ken-ichi Hanada, Yue A. Qi, Tapan Maity, Xu Zhang, Udayan Guha, Thorkell Andresson, James C. Yang
Summary: This article introduces a method of using mass spectrometry to identify common tumor-specific neoepitopes derived from mutated oncogenes, and develop TCRs based on these data. The results of the study show that this method successfully identified precise neoepitopes derived from KRAS, EGFR, BRAF, and PIK3CA presented by HLA-A*03:01 and/or HLA-A*11:01 across multiple biological replicates.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Immunology
Sarah A. Penny, Jennifer G. Abelin, Stacy A. Malaker, Paisley T. Myers, Abu Z. Saeed, Lora G. Steadman, Dina L. Bai, Stephen T. Ward, Jeffrey Shabanowitz, Donald F. Hunt, Mark Cobbold
Summary: The study found that in colorectal cancer, HLA-I phosphopeptides are important targets for immunotherapy, triggering tumor-resident immunity against malignancy. These phosphopeptides, derived from certain signaling pathways, can potentially lead to the development of broadly applicable therapeutic strategies.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Engineering, Multidisciplinary
Wenwen Wang, Lili Ma, Zheng Xing, Tinggan Yuan, Jinxia Bao, Yanjing Zhu, Xiaofang Zhao, Yan Zhao, Yali Zong, Yani Zhang, Siyun Shen, Xinyao Qiu, Shuai Yang, Hongyang Wang, Dong Gao, Peng Wang, Lei Chen
Summary: This study demonstrates the potential of circular RNAs (circRNAs) as a novel source of tumor antigen peptides in hepatobiliary tumor organoids. The circRNA-derived antigen peptides stimulate CD8 T cells and exhibit cytotoxic effects on tumor organoids.
Review
Oncology
Bing Zhang, Michal Bassani-Sternberg
Summary: Identification of tumor antigens presented by HLA molecules is crucial for cancer immunotherapies. MS-based immunopeptidomics enables high-throughput identification of HLA-bound peptides. Integrating DNA, RNA, and ribosome sequencing data allows identification of tumor antigens encoded within coding genes and non-coding regions. Computational challenges exist in immunopeptidomics data analysis and tumor antigen identification. Advancements in technology and computation are improving sensitivity and accuracy in tumor antigen identification.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Biochemistry & Molecular Biology
Rupert L. Mayer, Francis Impens
Summary: Immunopeptidomics is a promising approach for discovering bacterial epitopes presented on infected cells, which can be utilized in the development of next-generation vaccines, especially for intracellular bacterial pathogens. Challenges remain in the selection of bacterial antigens as vaccine candidates.
TRENDS IN MICROBIOLOGY
(2021)
Article
Biochemical Research Methods
Jenna Cleyle, Marie-Pierre Hardy, Robin Minati, Mathieu Courcelles, Chantal Durette, Joel Lanoix, Jean-Philippe Laverdure, Krystel Vincent, Claude Perreault, Pierre Thibault
Summary: This study identified tumor-specific antigens in colorectal cancer using a novel proteogenomic approach. The researchers found that many of these antigens originated from noncoding regions and could have therapeutic potential in various tumors. These findings are significant for the development of T cell-based vaccines and could improve treatment efficacy across subtypes of colorectal cancer when used in combination with existing immune checkpoint inhibition therapies.
MOLECULAR & CELLULAR PROTEOMICS
(2022)
Article
Multidisciplinary Sciences
Tamara Verkerk, Sofie J. Koomen, Kyra J. Fuchs, Marieke Griffioen, Robbert M. Spaapen
Summary: In the era of T cell-based immunotherapies, understanding the types of MHC-presented T cell antigens produced by tumor cells is crucial. This Perspective highlights the significance of knowing the contribution of chimeric peptides generated through proteasome-catalyzed peptide splicing (PCPS) and reviews methodologies for identifying MHC-presented spliced peptide antigens. The analysis shows that spliced peptides make only a marginal contribution to the pool of immunogenic tumor antigens, suggesting that they may not be a comprehensive source for expanding the number of targetable antigens in immunotherapies.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Oncology
Yae Kye, Lokesh Nagineni, Shrikanth Gadad, Fabiola Ramirez, Hannah Riva, Lorena Fernandez, Michelle Samaniego, Nathan Holland, Rose Yeh, Kei Takigawa, Subramanian Dhandayuthapani, Jessica Chacon
Summary: This review article emphasizes the process and importance of identifying neoantigens for immunotherapy for cancer, highlighting the potential of personalized cancer therapy and the challenges related to neoantigen identification and clinical application.
Article
Immunology
Shuhang Wang, Yuqi Yang, Lu Li, Peiwen Ma, Yale Jiang, Minghui Ge, Yue Yu, Huiyao Huang, Yuan Fang, Ning Jiang, Huilei Miao, Hao Guo, Linlin Yan, Yong Ren, Lichao Sun, Yan Zha, Ning Li
Summary: This study aimed to identify MESO antigens for mRNA vaccine development and determine immune subtypes for suitable patients. Five potential antigens for MESO were identified, and two immune subtypes were found. Furthermore, immune characteristics and genes related to these subtypes were analyzed. These findings have important implications for the development of new cancer treatment methods.
Article
Biochemical Research Methods
Cheryl F. Lichti
Summary: Proteasomal spliced peptides (PSPs) have been identified as novel neoantigens that can stimulate specific T cells in tumors. While some false positive PSPs arise from modified peptides, others may stem from data processing errors. The reported numbers of PSPs in the literature are likely inflated due to errors associated with data processing and analysis.
Article
Genetics & Heredity
Liguo Ye, Long Wang, Ji'an Yang, Ping Hu, Chunyu Zhang, Shi'ao Tong, Zhennan Liu, Daofeng Tian
Summary: This study identified two potential mRNA antigens for developing GBM mRNA vaccination, which were positively associated with antigen-presenting immune cells in GBM. Two robust immune subtypes in GBM, IS1 and IS2, had distinct clinical outcomes, with patients in IS2 considered the most suitable population for vaccination. The findings highlight the importance of immunophenotyping and identifying suitable tumor antigens for effective cancer vaccination strategies in GBM.
FRONTIERS IN GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Xing Huang, Tianyu Tang, Gang Zhang, Tingbo Liang
Summary: This study identified three potential tumor antigens associated with superior prognosis in cholangiocarcinoma and stratified cholangiocarcinoma patients into two immune subtypes based on molecular and clinical features. The findings provide a theoretical basis for the development of mRNA vaccines against cholangiocarcinoma and selection of suitable patients for vaccination.
Review
Immunology
Jonas P. Becker, Angelika B. Riemer
Summary: Immunopeptidomics is crucial for epitope-centric cancer immunotherapies, providing direct proof of cell surface presentation. Despite significant progress in the field, identification of HLA-presented peptides remains challenging.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Liguo Ye, Long Wang, Ji'an Yang, Ping Hu, Chunyu Zhang, Shi'ao Tong, Zhennan Liu, Daofeng Tian
Summary: This study identified four potential tumor antigens in LGG through genomic and clinical data analysis, and determined the most suitable population for cancer vaccination based on immunophenotyping. Three immune subtypes representing immune status desert, immune inhibition, and inflamed were identified, serving as predictive parameters.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Editorial Material
Oncology
Melita Irving, Vincent Zoete, Michal Bassani-Sternberg, George Coukos
Summary: In their comprehensive study, the researchers provide proof of principle for the development and efficacy of peptide centric (PC)-CARs targeting the oncogenic immunopeptidome of neuroblastoma.
Article
Biotechnology & Applied Microbiology
Marion Arnaud, Johanna Chiffelle, Raphael Genolet, Blanca Navarro Rodrigo, Marta A. S. Perez, Florian Huber, Morgane Magnin, Tu Nguyen-Ngoc, Philippe Guillaume, Petra Baumgaertner, Chloe Chong, Brian J. Stevenson, David Gfeller, Melita Irving, Daniel E. Speiser, Julien Schmidt, Vincent Zoete, Lana E. Kandalaft, Michal Bassani-Sternberg, Sara Bobisse, George Coukos, Alexandre Harari
Summary: NeoScreen is a method that enables sensitive identification of rare tumor antigens and corresponding T cell receptors, which can be used for personalized cancer vaccines and T cell therapies. T cells transduced with tumor antigen-specific TCRs identified by NeoScreen can regress established tumors in patient-derived xenograft mice.
NATURE BIOTECHNOLOGY
(2022)
Review
Oncology
Cheryl F. Lichti, Nathalie Vigneron, Karl R. Clauser, Benoit J. Van den Eynde, Michal Bassani-Sternberg
Summary: The topic of proteasomal spliced peptides (PSP) has generated controversy in the tumor immunology community. Early studies suggested PSP was rare, but recent analyses challenged this notion, leading to questions about the validity of the conclusions. It is proposed that a common set of standards should be established for validating candidate PSPs.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Oncology
Mona O. Mohsen, Daniel E. Speiser, Justine Michaux, HuiSong Pak, Brian J. Stevenson, Monique Vogel, Varghese Philipose Inchakalody, Simone de Brot, Said Dermime, Georges Coukos, Michal Bassani-Sternberg, Martin F. Bachmann
Summary: This study developed a multitarget vaccine using long neoantigenic peptides and virus-like particles as an efficient vaccine platform. The vaccination with long peptides showed superior anti-tumor effects and decreased tumor recurrence and metastases, despite the low mutational burden of the tumor.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Multidisciplinary Sciences
Abhijeet Pataskar, Julien Champagne, Remco Nagel, Juliana Kenski, Maarja Laos, Justine Michaux, Hui Song Pak, Onno B. Bleijerveld, Kelly Mordente, Jasmine Montenegro Navarro, Naomi Blommaert, Morten M. Nielsen, Domenica Lovecchio, Everett Stone, George Georgiou, Mark C. de Gooijer, Olaf van Tellingen, Maarten Altelaar, Robbie P. Joosten, Anastassis Perrakis, Johanna Olweus, Michal Bassani-Sternberg, Daniel S. Peeper, Reuven Agami
Summary: Activated T cells secrete interferon-gamma to trigger tryptophan depletion by increasing the activity of IDO1 enzyme. However, in-frame protein synthesis continues across tryptophan codons due to the reassignment of tryptophan-to-phenylalanine codons. These substitutants are highly abundant in multiple cancer types and are associated with increased IDO1 expression, oncogenic signaling, and the tumor-immune microenvironment.
Editorial Material
Oncology
Marion Arnaud, George Coukos, Alexandre Harari
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Immunology
Julien Racle, Philippe Guillaume, Julien Schmidt, Justine Michaux, Amede Larabi, Kelvin Lau, Marta A. S. Perez, Giancarlo Croce, Raphael Genolet, George Coukos, Vincent Zoete, Florence Pojer, Michal Bassani-Sternberg, Alexandre Harari, David Gfeller
Summary: In this study, a dataset of 627,013 unique MHC-II ligands identified by mass spectrometry was collected and curated, allowing for precise determination of binding motifs for 88 MHC-II alleles across different species. Further analysis revealed a reverse-binding mode in HLA-DP ligands, and a machine-learning framework was developed to accurately predict binding specificities and ligands of any MHC-II allele.
Review
Immunology
Ilja E. Shapiro, Michal Bassani-Sternberg
Summary: The immunopeptidome is a collection of peptides presented by MHC molecules on the surface of cells involved in T-cell immunosurveillance. It provides information about the cellular health state and is influenced by various factors. Immunopeptidomics is the method used to extract and analyze these peptides, giving insights into the immunopeptidome.
SEMINARS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Julien Schmidt, Johanna Chiffelle, Marta A. S. Perez, Morgane Magnin, Sara Bobisse, Marion Arnaud, Raphael Genolet, Julien Cesbron, David Barras, Blanca Navarro Rodrigo, Fabrizio Benedetti, Alexandra Michel, Lise Queiroz, Petra Baumgaertner, Philippe Guillaume, Michael Hebeisen, Olivier Michielin, Tu Nguyen-Ngoc, Florian Huber, Melita Irving, Stephanie Tissot-Renaud, Brian J. Stevenson, Sylvie Rusakiewicz, Denarda Dangaj Laniti, Michal Bassani-Sternberg, Nathalie Rufer, David Gfeller, Lana E. Kandalaft, Daniel E. Speiser, Vincent Zoete, George Coukos, Alexandre Harari
Summary: This study explores the functional and structural avidities of T cell clones specific for different antigens and finds that T cells from tumors have stronger functional and structural avidities compared to those from blood. Neoantigen-specific T cells have higher structural avidity and are preferentially detected in tumors. Based on these findings, the researchers develop an in silico model to predict TCR structural avidity and validate the enrichment of high avidity T cells in patients' tumors.
NATURE COMMUNICATIONS
(2023)
Article
Engineering, Biomedical
Patrick Reichenbach, Greta Maria Paola Giordano Attianese, Khaoula Ouchen, Elisabetta Cribioli, Melanie Triboulet, Sarah Ash, Margaux Saillard, Romain Vuillefroy de Silly, George Coukos, Melita Irving
Summary: This study reports the design and production of a lentiviral vector that incorporates two functionally independent promoters, allowing for the expression of a tumour-directed receptor and inducible gene in T cells. The vector enables the delivery of various genes to human T cells, improving the safety and efficacy of T-cell therapies.
NATURE BIOMEDICAL ENGINEERING
(2023)
Article
Oncology
Anne I. . Kraemer, Chloe Chong, Florian Huber, HuiSong Pak, Brian J. J. Stevenson, Markus Mueller, Justine Michaux, Emma Ricart Altimiras, Sylvie Rusakiewicz, Laia Simo-Riudalbas, Evarist Planet, Maciej Wiznerowicz, Julien Dagher, Didier Trono, George Coukos, Stephanie Tissot, Michal Bassani-Sternberg
Summary: A key barrier to improving personalized cancer immunotherapies is patient stratification. This study examines the differences in the immunopeptidome between highly inflamed and noninflamed tumors, and associates them with immune recognition. The findings have implications for tailored combination therapies based on the patient's mutanome and immune microenvironment.
Article
Immunology
Olga Zimmermannova, Alexandra G. Ferreira, Ervin Ascic, Marta Velasco Santiago, Ilia Kurochkin, Morten Hansen, Ozcan Met, Ines Caiado, Ilja E. Shapiro, Justine Michaux, Marion Humbert, Diego Soto-Cabrera, Hreinn Benonisson, Rita Silverio-Alves, David Gomez-Jimenez, Carina Bernardo, Monika Bauden, Roland Andersson, Mattias Hoglund, Kenichi Miharada, Yukio Nakamura, Stephanie Hugues, Lennart Greiff, Malin Lindstedt, Fabio F. Rosa, Cristiana F. Pires, Michal Bassani-Sternberg, Inge Marie Svane, Carlos-Filipe Pereira
Summary: Decreased antigen presentation allows cancer cells to escape from the immune system. Researchers successfully reprogrammed cancer cells into professional antigen-presenting cells (APCs) using the gene regulatory network of type 1 conventional dendritic cells (cDC1). This reprogramming restored the expression of antigen presentation complexes and costimulatory molecules, enabling the cancer cells to present tumor antigens and activate CD8(+) T cells for targeted killing. The reprogrammed tumor-APCs also showed impaired tumorigenicity and elicited synergistic antitumor immune responses with immune checkpoint inhibitors.
SCIENCE IMMUNOLOGY
(2023)
Article
Biochemical Research Methods
Xiaokang Li, Hui Song Pak, Florian Huber, Justine Michaux, Marie Taillandier-Coindard, Emma Ricart Altimiras, Michal Bassani-Sternberg
Summary: Mass spectrometry (MS)-based immunopeptidomics is an effective antigen discovery method for clinical applications. However, extracting HLA-restricted peptides from clinical specimens remains challenging. In this study, we present an innovative workflow that utilizes a low sample volume and a microfluidics platform to improve assay sensitivity. By employing data-independent acquisition (DIA), we identified thousands of HLA-I-restricted peptides from small sample sizes. This workflow is a powerful tool for identifying the immunopeptidome of sparse samples.
CELL REPORTS METHODS
(2023)
Review
Oncology
Lana E. Kandalaft, Denarda Dangaj Laniti, George Coukos
Summary: This review proposes a classification system based on immunophenotypes to explain the failures of existing immunotherapies in high-grade serous ovarian cancers, and suggests that rational therapeutic approaches tailored to each immunophenotype might meet with improved success.
NATURE REVIEWS CANCER
(2022)