Cancer-specific loss of p53 leads to a modulation of myeloid and T cell responses.
journal contributionposted on 23.01.2020 by Julianna Blagih, Fabio Zani, Probir Chakravarty, Marc Hennequart, Steven Pilley, Sebastijan Hobor, Andreas K Hock, Josephine B Walton, Jennifer P Morton, Eva Gronroos, Susan Mason, Ming Yang, Iain McNeish, Charles Swanton, Karen Blyth, Karen H Vousden
Any type of content formally published in an academic journal, usually following a peer-review process.
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.