TY - JOUR
TI - Lung tumor MHCII immunity depends on in situ antigen presentation by fibroblasts
AU - Kerdidani, D.
AU - Aerakis, E.
AU - Verrou, K.-M.
AU - Angelidis, I.
AU - Douka, K.
AU - Maniou, M.-A.
AU - Stamoulis, P.
AU - Goudevenou, K.
AU - Prados, A.
AU - Tzaferis, C.
AU - Ntafis, V.
AU - Vamvakaris, I.
AU - Kaniaris, E.
AU - Vachlas, K.
AU - Sepsas, E.
AU - Koutsopoulos, A.
AU - Potaris, K.
AU - Tsoumakidou, M.
JO - JOURNAL OF EXPERIMENTAL MEDICINE
PY - 2022
VL - 219
TODO - 2
SP - null
PB - Rockefeller University Press
SN - 0022-1007
TODO - 10.1084/jem.20210815
TODO - 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
TODO - 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.
ER -