Τίτλος:
Lung tumor MHCII immunity depends on in situ antigen presentation by fibroblasts
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Kerdidani, D.
Aerakis, E.
Verrou, K.-M.
Angelidis, I.
Douka, K.
Maniou, M.-A.
Stamoulis, P.
Goudevenou, K.
Prados, A.
Tzaferis, C.
Ntafis, V.
Vamvakaris, I.
Kaniaris, E.
Vachlas, K.
Sepsas, E.
Koutsopoulos, A.
Potaris, K.
Tsoumakidou, M.
Περιοδικό:
JOURNAL OF EXPERIMENTAL MEDICINE
Εκδότης:
Rockefeller University Press
Λέξεις-κλειδιά:
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
DOI:
10.1084/jem.20210815
