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

Blagih, J; Zani, F; Chakravarty, P; Hennequart, M; Pilley, S; Hobor, S; Hock, AK; ... Vousden, KH; + view all (2020) Cancer-Specific Loss of p53 Leads to a Modulation of Myeloid and T Cell Responses. Cell Reports , 30 (2) 481-496.e6. 10.1016/j.celrep.2019.12.028. Green open access

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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.

Type: Article
Title: Cancer-Specific Loss of p53 Leads to a Modulation of Myeloid and T Cell Responses
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2019.12.028
Publisher version: https://doi.org/10.1016/j.celrep.2019.12.028
Language: English
Additional information: Copyright © 2019 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Kras, T cell response, myeloid cells, p53, tumor
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10092842
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