Interleukin-1α release during necrotic-like cell death generates myeloid-driven immunosuppression that restricts anti-tumor immunity.

ABSTRACT: Necroptosis can promote antigen-specific immune responses, suggesting induced necroptosis as a therapeutic approach for cancer. Here we sought to determine the mechanism of immune activation but found the necroptosis mediators RIPK3 and MLKL dispensable for tumor growth in genetic and implantable models of breast or lung cancer. Surprisingly, inducing necroptosis within established breast tumors generates a myeloid suppressive microenvironment that inhibits T cell function, promotes tumor growth, and reduces survival. This was dependent upon the release of the nuclear alarmin interleukin-1α (IL-1α) by dying cells. Critically, IL-1α release occurs during chemotherapy and targeting this molecule reduces the immunosuppressive capacity of tumor myeloid cells and promotes CD8⁺ T cell

SUBMITTER: Hanggi K 

PROVIDER: S-EPMC11631672 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature