Cancer-specific loss of p53 leads to a modulation of myeloid and T cell responses
File(s)
Published version
Author(s)
Type
Journal Article
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.
Date Issued
2020-01-14
Date Acceptance
2019-12-06
Citation
Cell Reports, 2020, 30 (2), pp.481-196.e6
ISSN
2211-1247
Publisher
Elsevier
Start Page
481
End Page
196.e6
Journal / Book Title
Cell Reports
Volume
30
Issue
2
Copyright Statement
© 2019 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Sponsor
Imperial College Healthcare NHS Trust- BRC Funding
Cancer Research UK
Ovarian Cancer Action
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000507498100015&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
RDB01
RG71079
n/a
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
TUMOR-SUPPRESSOR P53
MACROPHAGES
PROMOTES
GROWTH
INFLAMMATION
PROGRESSION
IMMUNITY
BLOCKADE
RAS
MICROENVIRONMENT
Publication Status
Published
Date Publish Online
2020-01-14