Cancer-specific loss of p53 leads to a modulation of myeloid and T cell responses
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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 VousdenAbstract
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.
Journal details
Journal Cell Reports
Volume 30
Issue number 2
Pages 481-496.e6
Available online
Publication date
Full text links
Publisher website (DOI) 10.1016/j.celrep.2019.12.028
Figshare View on figshare
Europe PubMed Central 31940491
Pubmed 31940491