Immunogenomic Landscape of Neuroendocrine Prostate Cancer

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Neuroendocrine prostate cancer (NEPC) treatment often uses small-cell lung cancer (SCLC) immunotherapy protocols.
• Understanding NEPC's tumor immune landscape is crucial for optimizing treatment.

Purpose of the Study:

• To compare the tumor immune microenvironment of NEPC with other prostate cancer types and SCLC.
• To evaluate genomic alterations and their association with outcomes in prostate cancer.

Main Methods:

• Retrospective analysis of 170 patients with 230 RNA-sequencing and 104 whole-exome sequencing data.
• Evaluation of immune and stromal cell constituents and genomic alterations.
• Comparison of NEPC immune landscape with other prostate cancers and SCLC.

Main Results:

• 36% of prostate tumors were CD8+ T-cell inflamed; 64% were T-cell depleted.
• T-cell-inflamed tumors showed shorter overall survival.
• NEPC was the most immune-depleted prostate cancer type, with only 9 of 36 cases being T-cell inflamed.
• Inflamed NEPC cases showed enriched IFN gamma and PD-1 signaling.
• NEPC had less immune content and fewer mutations than SCLC, but comparable checkpoint gene expression.

Conclusions:

• NEPC typically presents with an immune-depleted tumor microenvironment.
• A minority of NEPC cases exhibit an inflamed immune phenotype.
• Findings may guide the development of novel immunotherapy strategies for advanced prostate cancer.