CD4 and prostate cancer: Despite the increase in CD4+ T cells within prostate cancer bone metastases, they are insensitive to immune checkpoint therapy, because CD4+ T cells differentiate into the Th17 rather than the Th1 line, mechanically because bone tumors promote osteoclast-mediated bone resorption, releasing TGF-β, which inhibits the development of the Th1 line (18).