Cancer-specific loss of p53 leads to a modulation of myeloid and T cell responses. 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 10779/crick.11697858.v1 https://crick.figshare.com/articles/journal_contribution/Cancer-specific_loss_of_p53_leads_to_a_modulation_of_myeloid_and_T_cell_responses_/11697858 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. 2020-01-23 13:40:01 Kras T cell response myeloid cells p53 tumor Vousden FC001557 Swanton FC001169 BRF-ack CB 0601 Biochemistry and Cell Biology