An analysis of biopsy samples from 124 men with metastatic castration-resistant prostate cancer (mCRPC) provides data on the relevance of genomic instability to the immunological landscape. Overall, 10 patients (8.1%) had defective mismatch repair (dMMR), which was also associated with greater T cell infiltration and higher PD-L1 expression. Researchers then compiled a set of dMMR signatures, based on the presence of mutations in genes associated with DNA repair processes. Associations between immune-related gene expression and this dMMR-associated phenotype were then explored: notably, a positive association was observed between the proportion of dMMR activity and total immune infiltrate. When data from multiple biopsy sites were pooled, specific associations were observed between dMMR and 12 immune-checkpoint-related genes, including PDL1, PDL2, and TIM3. These findings have implications for the development of immune-related biomarkers for patients with mCRPC.
Nava Rodrigues, D. et al. Immunogenomic analyses associate immunological alterations with mismatch repair defects in prostate cancer. J. Clin. Invest. https://doi.org/10.1172/JCI121924 (2018)
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Sidaway, P. Immunogenomic features of mCRPC revealed. Nat Rev Clin Oncol 15, 654 (2018). https://doi.org/10.1038/s41571-018-0098-8