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