In summary, our results demonstrated that a regulatory mechanism that inhibits AR signaling in primary prostate cancer through ADT might inhibit the tumor-suppressive role of AR, leading to the activation of CHRM4/AKT/MYCN signaling to promote IFNA17 secretion in the TME, which may be involved in stimulating immune checkpoint pathway components in a subset of prostate cancer patients with NE characteristics (Fig. 7L). Here, CHRM4 is linked to prostate cancer.