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The view that androgen deprivation uniformly enhances antitumor immunity does not explain the repeated failure of immunotherapy combinations in biomarker\u2010unselected populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This narrative review synthesizes mechanistic, translational, and clinical evidence and organizes it by cellular compartment, treatment\u2010associated immune state, clinical trial strategy, and biomarker readiness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>AR\u2010directed therapy produces context\u2010dependent, compartment\u2010specific immune remodeling. It can alter tumor antigen visibility, thymic output, and T\u2010cell trafficking, while myeloid cytokines and metabolites, cancer\u2010associated fibroblasts, and metastatic niches sustain AR reactivation, T\u2010cell dysfunction, and immune exclusion. These effects are better understood as heterogeneous tumor\u2010immune states than as a fixed treatment window. Randomized phase III trials combining checkpoint blockade with AR pathway inhibitors, PARP inhibitors, or chemotherapy have not improved overall survival in unselected mCRPC, and dual\u2010checkpoint blockade has shown limited activity with substantial toxicity. Deficient mismatch repair or microsatellite instability\u2010high (dMMR\/MSI\u2010H) disease is currently the only clinically validated enrichment factor for checkpoint blockade in mCRPC, although this subgroup is uncommon. Composite signatures remain investigational. CDK12, homologous\u2010recombination repair alterations, isolated tumor mutational burden\u2010high disease, PD\u2010L1, and AR\u2010V7 are not independently validated selection markers. T\u2010cell engagers have produced early PSA and radiographic responses by providing a distinct route to tumor\u2010T\u2010cell contact. Their development must balance this activity against cytokine\u2010release syndrome, antigen heterogeneity, variable therapeutic windows, and the lack of comparative evidence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Progress requires trials that define the relevant tumor\u2010immune state, match treatment to the dominant resistance mechanism, and prospectively test biomarker\u2010treatment interaction. In current practice, dMMR\/MSI\u2010H remains the only validated enrichment factor for checkpoint blockade in mCRPC; all other proposed markers and T\u2010cell engager strategies require prospective validation of treatment interaction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pros.70254","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:41:01Z","timestamp":1790534461000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Androgen Receptor\u2010Immune Crosstalk in Metastatic Castration\u2010Resistant Prostate Cancer: From Context\u2010Dependent Remodeling to Biomarker\u2010Guided Translation"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1270-5721","authenticated-orcid":false,"given":"Linjie","family":"Li","sequence":"first","affiliation":[{"name":"Department of Urology The First Affiliated Hospital of Chongqing Medical University 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