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Kerdidani D, Aerakis E, Verrou KM, et al. Lung tumor MHCII immunity depends on in situ antigen presentation by fibroblasts. J Exp Med. 2022;219(2)doi: 10.1084/jem.20210815.
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. (2022). Lung tumor MHCII immunity depends on in situ antigen presentation by fibroblasts. The Journal of experimental medicine, 219(2), . https://doi.org/10.1084/jem.20210815
Kerdidani, Dimitra, et al. "Lung tumor MHCII immunity depends on in situ antigen presentation by fibroblasts." The Journal of experimental medicine vol. 219,2 (2022). doi: https://doi.org/10.1084/jem.20210815
Kerdidani D, Aerakis E, Verrou KM, Angelidis I, Douka K, Maniou MA, Stamoulis P, Goudevenou K, Prados A, Tzaferis C, Ntafis V, Vamvakaris I, Kaniaris E, Vachlas K, Sepsas E, Koutsopoulos A, Potaris K, Tsoumakidou M. Lung tumor MHCII immunity depends on in situ antigen presentation by fibroblasts. J Exp Med. 2022 Feb 07;219(2). doi: 10.1084/jem.20210815. Epub 2022 Jan 14. PMID: 35029648.
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J Exp Med. 2022 Feb 07;219(2). doi: 10.1084/jem.20210815. Epub 2022 Jan 14.

Lung tumor MHCII immunity depends on in situ antigen presentation by fibroblasts.

The Journal of experimental medicine

Dimitra Kerdidani, Emmanouil Aerakis, Kleio-Maria Verrou, Ilias Angelidis, Katerina Douka, Maria-Anna Maniou, Petros Stamoulis, Katerina Goudevenou, Alejandro Prados, Christos Tzaferis, Vasileios Ntafis, Ioannis Vamvakaris, Evangelos Kaniaris, Konstantinos Vachlas, Evangelos Sepsas, Anastasios Koutsopoulos, Konstantinos Potaris, Maria Tsoumakidou

Affiliations

  1. Institute of Bioinnovation, Biomedical Sciences Research Center "Alexander Fleming," Vari, Greece.
  2. Greek Research Infrastructure for Personalized Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
  3. Animal House Facility, Biomedical Sciences Research Center "Alexander Fleming," Vari, Greece.
  4. Department of Pathology, Sotiria Chest Hospital, Athens, Greece.
  5. Department of Respiratory Medicine, Sotiria Chest Hospital, Athens, Greece.
  6. Department of Thoracic Surgery, Sotiria Chest Hospital, Athens, Greece.
  7. Department of Pathology, Medical School, University of Crete, Crete, Greece.

PMID: 35029648 DOI: 10.1084/jem.20210815

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.

Conflict of interest statement

Disclosures: The authors declare no competing interests exist.

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