Extended Data Fig. 10: Pharmacological inhibition of IL-23 in association with ADT delays disease progression in prostate cancer.
From: IL-23 secreted by myeloid cells drives castration-resistant prostate cancer
a, Haematoxylin and eosin and Ki-67 immunohistochemical staining (Ki-67, brown; nuclei, blue) of representative castrated PtenPC−/− mice treated with IL-23, ENZA or both. Scale bars, 50 μm. b, Quantification of Ki-67 reported as a percentage of total within the glands. One tumour per mouse, three sections per tumour, ≥3 fields per section. Data are mean ± s.e.m. of biologically independent animals. Untreated, n = 6; IL-23, n = 6; ENZA, n = 5 or both, n = 6. Statistical analyses (unpaired two-sided Student’s t-test): **P < 0.01; ***P < 0.001. c, After castration, PMN-MDSCs progressively infiltrate the tumour bed mainly recruited by CXCL5. Within the tumour, PMN-MDSCs start to produce higher amount of IL-23, thus establishing a positive-feedback loop that induces the overexpression of IL-23R on the tumour epithelial cells and confer resistance to castration in prostate cancer by activating the STAT3–RORγ pathway. ENZA treatment can block the AR, inducing sensitiveness of prostate cancer cells to androgen deprivation, but the persistent presence of PMN-MDSC-derived IL-23 rescues the drug sensitiveness leading to ADT resistance. Anti-IL-23 treatment reinstates sensitivity to castration in prostate cancer enhancing the efficacy of ENZA.
