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：

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

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

共 76 条

[1] Oncogenic Ras-induced expression of cytokines: A new target of anti-cancer therapeutics [J].

Ancrile, Brooke B. ;

O'Hayer, Kevin M. ;

Counter, Christopher M. .

MOLECULAR INTERVENTIONS, 2008, 8 (01) :22-27

[2]

[Anonymous], FASEB J

[3] A Distinct Function of Regulatory T Cells in Tissue Protection [J].

Arpaia, Nicholas ;

Green, Jesse A. ;

Moltedo, Bruno ;

Arvey, Aaron ;

Hemmers, Saskia ;

Yuan, Shaopeng ;

Treuting, Piper M. ;

Rudensky, Alexander Y. .

CELL, 2015, 162 (05) :1078-1089

[4] Sustained IL-12 signaling is required for Th1 development [J].

Athie-Morales, V ;

Smits, HH ;

Cantrell, DA ;

Hilkens, CMU .

JOURNAL OF IMMUNOLOGY, 2004, 172 (01) :61-69

[5] QuPath: Open source software for digital pathology image analysis [J].

Bankhead, Peter ;

Loughrey, Maurice B. ;

Fernandez, Jose A. ;

Dombrowski, Yvonne ;

Mcart, Darragh G. ;

Dunne, Philip D. ;

McQuaid, Stephen ;

Gray, Ronan T. ;

Murray, Liam J. ;

Coleman, Helen G. ;

James, Jacqueline A. ;

Salto-Tellez, Manuel ;

Hamilton, Peter W. .

SCIENTIFIC REPORTS, 2017, 7

[6] MACROPHAGES SPECIFICALLY REGULATE THE CONCENTRATION OF THEIR OWN GROWTH-FACTOR IN THE CIRCULATION [J].

BARTOCCI, A ;

MASTROGIANNIS, DS ;

MIGLIORATI, G ;

STOCKERT, RJ ;

WOLKOFF, AW ;

STANLEY, ER .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (17) :6179-6183

[7] Tumor-Derived Granulocyte-Macrophage Colony-Stimulating Factor Regulates Myeloid Inflammation and T Cell Immunity in Pancreatic Cancer [J].

Bayne, Lauren J. ;

Beatty, Gregory L. ;

Jhala, Nirag ;

Clark, Carolyn E. ;

Rhim, Andrew D. ;

Stanger, Ben Z. ;

Vonderheide, Robert H. .

CANCER CELL, 2012, 21 (06) :822-835

[8] The Macrophage Colony-Stimulating Factor 1 Response Signature in Breast Carcinoma [J].

Beck, Andrew H. ;

Espinosa, Inigo ;

Edris, Badreddin ;

Li, Rui ;

Montgomery, Kelli ;

Zhu, Shirley ;

Varma, Sushama ;

Marinelli, Robert J. ;

van de Rijn, Matt ;

West, Robert B. .

CLINICAL CANCER RESEARCH, 2009, 15 (03) :778-787

[9] Diverse genetic-driven immune landscapes dictate tumor progression through distinct mechanisms [J].

Bezzi, Marco ;

Seitzer, Nina ;

Ishikawa, Tomoki ;

Reschke, Markus ;

Chen, Ming ;

Wang, Guocan ;

Mitchell, Caitlin ;

Ng, Christopher ;

Katon, Jesse ;

Lunardi, Andrea ;

Signoretti, Sabina ;

Clohessy, John G. ;

Zhang, Jiangwen ;

Pandolfi, Pier Paolo .

NATURE MEDICINE, 2018, 24 (02) :165-+

[10] CSF1R+ Macrophages Sustain Pancreatic Tumor Growth through T Cell Suppression and Maintenance of Key Gene Programs that Define the Squamous Subtype [J].

Candido, Juliana B. ;

Morton, Jennifer P. ;

Bailey, Peter ;

Campbell, Andrew D. ;

Karim, Saadia A. ;

Jamieson, Thomas ;

Lapienyte, Laura ;

Gopinathan, Aarthi ;

Clark, William ;

McGhee, Ewan J. ;

Wang, Jun ;

Escorcio-Correia, Monica ;

Zollinger, Raphael ;

Roshani, Rozita ;

Drew, Lisa ;

Rishi, Loveena ;

Arkell, Rebecca ;

Evans, T. R. Jeffry ;

Nixon, Colin ;

Jodrell, Duncan I. ;

Wilkinson, Robert W. ;

Biankin, Andrew V. ;

Barry, Simon T. ;

Balkwill, Frances R. ;

Sansom, Owen J. .

CELL REPORTS, 2018, 23 (05) :1448-1460

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