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Autonomous IL-36R Signaling positively modulates Neutrophil Anti-tumor Effector Functions

ABSTRACT: Despite the cancer treatment revolution brought on by the rapid advancement of immunotherapies, only a small fraction of patients derive clinical benefit. Moreover, eradication of large established tumors requires a concerted effort of complete immune system and hence identifying agents that activate and interlink both innate and adaptive immune system components is required. Here, we report that IL-36 cytokine can remodel an immune-suppressive tumor microenvironment (TME) and mediate potent anti-tumor immune response through hematopoietic cells, via both innate and adaptive immunity. Further, we demonstrate that IL-36 signaling reprograms neutrophils in a cell-intrinsic manner to greatly enhances their ability to directly kill tumor cells, their antigen presentation capability and promote T cell proliferation. Thus, the pleotropic effects of IL-36 transform neutrophils into potent effector cells to promote tumor rejection. While poor prognostic outcomes are associated with neutrophil enhancement in the TME, our results highlight the therapeutic potential of harnessing the ability of IL-36 signaling to reprogram neutrophils and link innate and adaptive immune system to enhance durable anti-tumor responses in solid tumors.

ORGANISM(S): Mus musculus

PROVIDER: GSE210120 | GEO | 2023/06/21

REPOSITORIES: GEO

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