@article{3118573,
    title = "Lung tumor MHCII immunity depends on in situ antigen presentation by fibroblasts",
    author = "Kerdidani, D. and Aerakis, E. and Verrou, K.-M. and Angelidis, I. and Douka, K. and Maniou, M.-A. and Stamoulis, P. and Goudevenou, K. and Prados, A. and Tzaferis, C. and Ntafis, V. and Vamvakaris, I. and Kaniaris, E. and Vachlas, K. and Sepsas, E. and Koutsopoulos, A. and Potaris, K. and Tsoumakidou, M.",
    journal = "JOURNAL OF EXPERIMENTAL MEDICINE",
    year = "2022",
    volume = "219",
    number = "2",
    publisher = "Rockefeller University Press",
    issn = "0022-1007",
    doi = "10.1084/jem.20210815",
    keywords = "C1QBP protein, human;  carrier protein;  gamma interferon;  HLA antigen class 2;  mitochondrial protein;  transcriptome;  tumor antigen, animal;  antigen presentation;  apoptosis;  cancer associated fibroblast;  disease model;  human;  immunology;  lung tumor;  lymphocyte activation;  lymphocyte count;  metabolism;  mouse;  pathology;  single cell analysis;  T lymphocyte subpopulation;  tumor associated leukocyte;  tumor microenvironment, Animals;  Antigen Presentation;  Antigens, Neoplasm;  Apoptosis;  Cancer-Associated Fibroblasts;  Carrier Proteins;  Disease Models, Animal;  Histocompatibility Antigens Class II;  Humans;  Interferon-gamma;  Lung Neoplasms;  Lymphocyte Activation;  Lymphocyte Count;  Lymphocytes, Tumor-Infiltrating;  Mice;  Mitochondrial Proteins;  Single-Cell Analysis;  T-Lymphocyte Subsets;  Transcriptome;  Tumor Microenvironment",
    abstract = "A key unknown of the functional space in tumor immunity is whether CD4 T cells depend on intratumoral MHCII cancer antigen recognition. MHCII-expressing, antigen-presenting cancer-associated fibroblasts (apCAFs) have been found in breast and pancreatic tumors and are considered to be immunosuppressive. This analysis shows that antigen-presenting fibroblasts are frequent in human lung non-small cell carcinomas, where they seem to actively promote rather than suppress MHCII immunity. Lung apCAFs directly activated the TCRs of effector CD4 T cells and at the same time produced C1q, which acted on T cell C1qbp to rescue them from apoptosis. Fibroblast-specific MHCII or C1q deletion impaired CD4 T cell immunity and accelerated tumor growth, while inducing C1qbp in adoptively transferred CD4 T cells expanded their numbers and reduced tumors. Collectively, we have characterized in the lungs a subset of antigen-presenting fibroblasts with tumor-suppressive properties and propose that cancer immunotherapies might be strongly dependent on in situ MHCII antigen presentation. © 2022 Kerdidani et al."
}