Cancer-Specific Loss of p53 Leads to a Modulation of Myeloid and T Cell Responses.
Cell Rep
; 30(2): 481-496.e6, 2020 01 14.
Article
en En
| MEDLINE
| ID: mdl-31940491
ABSTRACT
Loss of p53 function contributes to the development of many cancers. While cell-autonomous consequences of p53 mutation have been studied extensively, the role of p53 in regulating the anti-tumor immune response is still poorly understood. Here, we show that loss of p53 in cancer cells modulates the tumor-immune landscape to circumvent immune destruction. Deletion of p53 promotes the recruitment and instruction of suppressive myeloid CD11b+ cells, in part through increased expression of CXCR3/CCR2-associated chemokines and macrophage colony-stimulating factor (M-CSF), and attenuates the CD4+ T helper 1 (Th1) and CD8+ T cell responses in vivo. p53-null tumors also show an accumulation of suppressive regulatory T (Treg) cells. Finally, we show that two key drivers of tumorigenesis, activation of KRAS and deletion of p53, cooperate to promote immune tolerance.
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Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Proteína p53 Supresora de Tumor
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Linfocitos T Reguladores
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Células Mieloides
Idioma:
En
Revista:
Cell Rep
Año:
2020
Tipo del documento:
Article