Targeting CXCR2 in prostate cancer cells can block CD47-SIRPα interaction and reverse M2 macrophage polarization in the TME.

ABSTRACT: Neuroendocrine prostate cancer (NEPC) exhibits strong immune evasion and plays a critical role in regulating metabolic reprogramming within prostate cancer. High infiltration of CD36 + M2 tumour-associated macrophages (TAMs) and elevated CD47 expression in NEPC cells are often associated with poor progression-free survival in cancer patients. Understanding the mechanisms that regulate CD36 + M2 TAM infiltration and high CD47 expression in tumour cells within the prostate cancer tumour microenvironment (TME) is essential. Using cell models and two animal models, we discovered that the IL-8/CXCR2 pathway increases acetyl-CoA levels through metabolic reprogramming, which subsequently increases CD47 expression via acetylation. Moreover, this pathway modulates the membrane localization of CD47

SUBMITTER: Sun Y 

PROVIDER: S-EPMC12574227 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature