Evolution of myeloid-mediated immunotherapy resistance in prostate cancer.

ABSTRACT: Patients with advanced metastatic castration-resistant prostate cancer (mCRPC) are refractory to immune checkpoint inhibitors (ICIs)^1,2, partly because there are immunosuppressive myeloid cells in tumours^3,4. However, the heterogeneity of myeloid cells has made them difficult to target, making blockade of the colony stimulating factor-1 receptor (CSF1R) clinically ineffective. Here we use single-cell profiling on patient biopsies across the disease continuum and find that a distinct population of tumour-associated macrophages with elevated levels of SPP1 transcripts (SPP1^hi-TAMs) becomes enriched with the progression of prostate cancer to mCRPC. In syngeneic mouse modelling, an analogous macrophage population suppresses CD8⁺ T cell activity in vi

SUBMITTER: Lyu A 

PROVIDER: S-EPMC11779626 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature