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1.
Immunity ; 55(10): 1758-1760, 2022 10 11.
Artículo en Inglés | MEDLINE | ID: mdl-36223724

RESUMEN

The spectrum and origin of commensal bacterial HLA epitopes is not well understood. In this issue of Immunity, Pedersen et al. provide a systematic analysis of commensal bacterial HLA II epitopes and demonstrate plasticity of corresponding CD4+ T cell responses.


Asunto(s)
Linfocitos T CD4-Positivos , Epítopos de Linfocito T
2.
Immunity ; 55(4): 701-717.e7, 2022 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-35364006

RESUMEN

Bacterial sensing by intestinal tumor cells contributes to tumor growth through cell-intrinsic activation of the calcineurin-NFAT axis, but the role of this pathway in other intestinal cells remains unclear. Here, we found that myeloid-specific deletion of calcineurin in mice activated protective CD8+ T cell responses and inhibited colorectal cancer (CRC) growth. Microbial sensing by myeloid cells promoted calcineurin- and NFAT-dependent interleukin 6 (IL-6) release, expression of the co-inhibitory molecules B7H3 and B7H4 by tumor cells, and inhibition of CD8+ T cell-dependent anti-tumor immunity. Accordingly, targeting members of this pathway activated protective CD8+ T cell responses and inhibited primary and metastatic CRC growth. B7H3 and B7H4 were expressed by the majority of human primary CRCs and metastases, which was associated with low numbers of tumor-infiltrating CD8+ T cells and poor survival. Therefore, a microbiota-, calcineurin-, and B7H3/B7H4-dependent pathway controls anti-tumor immunity, revealing additional targets for immune checkpoint inhibition in microsatellite-stable CRC.


Asunto(s)
Neoplasias Colorrectales , Microbiota , Animales , Antígenos B7 , Linfocitos T CD8-positivos , Calcineurina/metabolismo , Neoplasias Colorrectales/metabolismo , Ratones , Factores de Transcripción NFATC/metabolismo , Inhibidor 1 de la Activación de Células T con Dominio V-Set
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