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Re-education of tumor-associated macrophages by CXCR2 blockade drives senescence and tumor inhibition in advanced prostate cancer

ABSTRACT: Tumor-associated macrophages (TAMs) represent a major component of the tumor microenvironment that supports tumorigenesis. Here we found that prostate tumors are strongly infiltrated by TAMs expressing the C-X-C chemokine receptor type 2 (CXCR2). Pharmacological blockade of the CXCR2 receptor by a selective antagonist promoted the re-education of TAMs towards a pro-inflammatory phenotype. Strikingly, CXCR2 knockout monocytes infused in Ptenpc-/-; Trp53pc-/- mice preferentially differentiatied in TNFα-releasing pro-inflammatory macrophages leading to senescence induction and tumor inhibition. Moreover, tumor cells harboring PTEN deletion were more sensitive to TNFα-induced senescence, when compared to PTEN WT tumors, due to increased levels of TNFR1. Our results identify TAMs as a target in prostate cancer therapy and describe a novel therapeutic strategy based on CXCR2 blockade to harness the anti-tumorigenic potential of macrophages against this disease.

ORGANISM(S): Mus musculus

PROVIDER: GSE124058 | GEO | 2019/12/10

REPOSITORIES: GEO

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Re-education of tumor-associated macrophages by CXCR2 blockade drives senescence and tumor inhibition in advanced prostate cancer

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