Cancer-specific loss of p53 leads to a modulation of myeloid and T cell responses

Blagih, J. et al. (2020) Cancer-specific loss of p53 leads to a modulation of myeloid and T cell responses. Cell Reports, 30(2), 481-496.e6. (doi: 10.1016/j.celrep.2019.12.028) (PMID:31940491) (PMCID:31940491)

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. [Abstract copyright: Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.]

• Item Type: Articles
• Keywords: Kras, T cell response, myeloid cells, p53, tumor
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Blyth, Professor Karen and Hock, Dr Andreas and Walton, Miss Josephine and Mcneish, Professor Iain and Vousden, Karen and Morton, Professor Jen and Mason, Miss Susan
• Authors: Blagih, J., Zani, F., Chakravarty, P., Hennequart, M., Pilley, S., Hobor, S., Hock, A. K., Walton, J. B., Morton, J. P., Gronroos, E., Mason, S., Yang, M., Mcneish, I., Swanton, C., Blyth, K., and Vousden, K.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cell Reports
• Publisher: Elsevier (Cell Press)
• ISSN: 2211-1247
• ISSN (Online): 2211-1247
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in Cell Reports 30:481-496
• Publisher Policy: Reproduced under a Creative Commons License