Cell Reports
Volume 30, Issue 2, 14 January 2020, Pages 481-496.e6
Journal home page for Cell Reports

Article
Cancer-Specific Loss of p53 Leads to a Modulation of Myeloid and T Cell Responses

https://doi.org/10.1016/j.celrep.2019.12.028Get rights and content
Under a Creative Commons license
open access

Highlights

  • Tumor-specific loss of p53 delays tumor rejection in immune-competent hosts

  • p53 loss increases myeloid infiltration through enhanced cytokine secretion

  • The increase in Treg cells in response to loss of p53 is independent of Kras mutation

  • Kras mutations coordinate with p53 loss to regulate myeloid recruitment

Summary

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.

Keywords

p53
Kras
tumor
myeloid cells
T cell response

Cited by (0)

6

Lead Contact