Loading
Life sciences · Journal article
The Prostate · September 27, 2026
No summary has been generated for this record yet. What follows is drawn from its source metadata only.
Journal article.
No findings were extractable from the material analysed.
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
The source did not state who this applies to in practice.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
This record has not been graded across any dimension yet. Treat the label above as provisional and read the source.
What is missing. This record has no bottom line, key findings, reported figures, evidence dimensions. That is a gap in the analysis, not a judgement about the study.
ABSTRACT Background Metastatic castration‐resistant prostate cancer (mCRPC) rarely responds to immune checkpoint blockade despite clear evidence that androgen receptor (AR) signaling intersects with tumor immunity. The view that androgen deprivation uniformly enhances antitumor immunity does not explain the repeated failure of immunotherapy combinations in biomarker‐unselected populations. Methods This narrative review synthesizes mechanistic, translational, and clinical evidence and organizes it by cellular compartment, treatment‐associated immune state, clinical trial strategy, and biomarker readiness. Results AR‐directed therapy produces context‐dependent, compartment‐specific immune remodeling. It can alter tumor antigen visibility, thymic output, and T‐cell trafficking, while myeloid cytokines and metabolites, cancer‐associated fibroblasts, and metastatic niches sustain AR reactivation, T‐cell dysfunction, and immune exclusion. These effects are better understood as heterogeneous tumor‐immune 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‐checkpoint blockade has shown limited activity with substantial toxicity. Deficient mismatch repair or microsatellite instability‐high (dMMR/MSI‐H) 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‐recombination repair alterations, isolated tumor mutational burden‐high disease, PD‐L1, and AR‐V7 are not independently validated selection markers. T‐cell engagers have produced early PSA and radiographic responses by providing a distinct route to tumor‐T‐cell contact. Their development must balance this activity against cytokine‐release syndrome, antigen heterogeneity, variable therapeutic windows, and the lack of comparative evidence. Conclusions Progress requires trials that define the relevant tumor‐immune state, match treatment to the dominant resistance mechanism, and prospectively test biomarker‐treatment interaction. In current practice, dMMR/MSI‐H remains the only validated enrichment factor for checkpoint blockade in mCRPC; all other proposed markers and T‐cell engager strategies require prospective validation of treatment interaction.