Genomic Profiling and Immune Phenotyping of Neuroendocrine Bladder Cancer - Expert Commentary
The researchers analyzed 35 NEBC cases through genomic analysis of 19 samples, transcriptomic analysis of 3 samples, single-cell RNA sequencing of 1 sample, and IHC analyses of 34 samples. Their findings revealed that despite a high mutational burden, NEBC showed immunologically inactive profiles. Unexpectedly, most tumors displayed either "immune-excluded" (41.2%) or "immune-desert" (26.5%) phenotypes, while mixed NEBC with concurrent urothelial bladder cancer showed an "immune-infiltrated" phenotype (32.3%) with better prognosis.
As a potential explanation, NEBC demonstrated denser cellular composition and enhanced peritumoral extracellular matrix compared to urothelial bladder cancer. Single-agent immune checkpoint inhibitors showed limited efficacy, while combination chemoimmunotherapy demonstrated improved response rates.
This study provides critical insights into NEBC immune biology. It suggests that combination chemoimmunotherapy is a promising therapeutic strategy warranting further investigation through prospective trials for patients with this aggressive disease.
Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine
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