https://www.selleckchem.com/pd-1-pd-l1.html Introduction Within the last decade, multiple innovative immune platforms have been developed and tested in patients with metastatic castration-resistant prostate cancer (mCRPC) with only one demonstrating a survival benefit. The advent of immunogenomics along with the availability of diverse checkpoint inhibitors provides inroads in treating these patients, in many cases with significant clinical impact but unfortunately not in all patients. How to exploit these novel platforms remains an area of increased interest especially in the setting of new agents that can affect the tumor microenvironment and potentially render a 'cold' tumor to become 'hot.'Areas covered This review highlights the current changes and challenges in this field and how to best use our current knowledge for better trial designs in patients with mCRPC.Expert opinion Recent understanding of the inhibitory milieu within the tumor microenvironment has fostered the use of combinatorial strategies that target not only tumor cells but capitalize on controlling inhibitory cell populations and cytokines that induce a hostile setting for immune cells. Immunogenomics and genomic interrogation of prostate cancers have opened a vista as to how patients' tumors that can respond to immune agents that previously were thought have minimal antitumor activity.When environmental variation is spatially continuous, dispersing individuals move among nearby sites with similar habitat conditions. But as an environmental gradient becomes steeper, gene flow may connect more divergent habitats, and this is predicted to reduce the slope of the adaptive cline that evolves. We compared quantitative genetic divergence of Rana temporaria frog populations along a 2,000-m elevational gradient in eastern Switzerland (new experimental results) with divergence along a 1,550-km latitudinal gradient in Fennoscandia (previously published results). Both studies found significant countergradi