Protein kinase C delta regulates mononuclear phagocytes and hinders response to immunotherapy in cancer.

ABSTRACT: Mononuclear phagocytes (MPs) play a crucial role in tissue homeostasis; however, MPs also contribute to tumor progression and resistance to immune checkpoint blockade (ICB). Targeting MPs could be an effective strategy to enhance ICB efficacy. We report that protein kinase C delta (PKCδ), a serine/threonine kinase, is abundantly expressed by MPs in human and mouse tumors. PKCδ^-/- mice displayed reduced tumor progression compared to wild types, with increased response to anti-PD-1. Tumors from PKCδ^-/- mice demonstrated T_H1-skewed immune response including increased antigen presentation and T cell activation. Depletion of MPs in vivo altered tumor growth in control but not PKCδ^-/- mice. Coinjection of PKCδ^-/- M2-like macrophages with can

SUBMITTER: Chaib M 

PROVIDER: S-EPMC10745701 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature