PIKfyve, expressed by CD11c-positive cells, controls tumor immunity.

ABSTRACT: Cancer treatment continues to shift from utilizing traditional therapies to targeted ones, such as protein kinase inhibitors and immunotherapy. Mobilizing dendritic cells (DC) and other myeloid cells with antigen presenting and cancer cell killing capacities is an attractive but not fully exploited approach. Here, we show that PIKFYVE is a shared gene target of clinically relevant protein kinase inhibitors and high expression of this gene in DCs is associated with poor patient response to immune checkpoint blockade (ICB) therapy. Genetic and pharmacological studies demonstrate that PIKfyve ablation enhances the function of CD11c⁺ cells (predominantly dendritic cells) via selectively altering the non-canonical NF-κB pathway. Both loss of Pikfyve in CD11c⁺ cells and tre

SUBMITTER: Choi JE 

PROVIDER: S-EPMC11213953 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature