Lung tumor MHCII immunity depends on in situ antigen presentation by fibroblasts.
J Exp Med
; 219(2)2022 02 07.
Article
en En
| MEDLINE
| ID: mdl-35029648
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antígenos de Histocompatibilidad Clase II
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Presentación de Antígeno
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Fibroblastos Asociados al Cáncer
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Neoplasias Pulmonares
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Antígenos de Neoplasias
Límite:
Animals
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Humans
Idioma:
En
Revista:
J Exp Med
Año:
2022
Tipo del documento:
Article
País de afiliación:
Grecia
Pais de publicación:
Estados Unidos