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

被引：133

作者：

Blagih, Julianne ^{[1
]}

Zani, Fabio ^{[1
]}

Chakravarty, Probir ^{[1
]}

Hennequart, Marc ^{[1
]}

Pilley, Steven ^{[1
]}

Hobor, Sebastijan ^{[1
]}

Hock, Andreas K. ^{[2
,4
]}

Walton, Josephine B. ^{[3
]}

Morton, Jennifer P. ^{[2
,3
]}

Gronroos, Eva ^{[1
]}

Mason, Susan ^{[2
]}

Yang, Ming ^{[1
]}

McNeish, Iain ^{[3
,5
]}

Swanton, Charles ^{[1
]}

Blyth, Karen ^{[2
,3
]}

Vousden, Karen H. ^{[1
]}

机构：

[1] Francis Crick Inst, 1 Midland Rd, London NW1 1AT, England

[2] Canc Res UK Beatson Inst, Switchback Rd, Glasgow G61 1BD, Lanark, Scotland

[3] Univ Glasgow, Inst Canc Sci, Garscube Estate, Glasgow G61 1QH, Lanark, Scotland

[4] AstraZeneca, R&D BioPharmaceut, Discovery Sci, Cambridge CB4 0WG, England

[5] Imperial Coll London, Ovarian Canc Act Res Ctr, Dept Surg & Canc, London W12 0NN, England

来源：

CELL REPORTS | 2020年 / 30卷 / 02期

基金：

英国医学研究理事会; 欧洲研究理事会; 欧盟地平线“2020”; 英国惠康基金;

关键词：

TUMOR-SUPPRESSOR P53; MACROPHAGES; PROMOTES; GROWTH; INFLAMMATION; PROGRESSION; IMMUNITY; BLOCKADE; RAS; MICROENVIRONMENT;

D O I：

10.1016/j.celrep.2019.12.028

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 tumor-igenesis, activation of KRAS and deletion of p53, cooperate to promote immune tolerance.

引用

页码：481 / +

页数：22

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