Data from Immunogenomic Landscape of Neuroendocrine Prostate Cancer

Abstract

<div>AbstractPurpose:<p>Patients with neuroendocrine prostate cancer (NEPC) are often managed with immunotherapy regimens extrapolated from small-cell lung cancer (SCLC). We sought to evaluate the tumor immune landscape of NEPC compared with other prostate cancer types and SCLC.</p>Experimental Design:<p>In this retrospective study, a cohort of 170 patients with 230 RNA-sequencing and 104 matched whole-exome sequencing data were analyzed. Differences in immune and stromal constituents, frequency of genomic alterations, and associations with outcomes were evaluated.</p>Results:<p>In our cohort, 36% of the prostate tumors were identified as CD8<sup>+</sup> T-cell inflamed, whereas the remaining 64% were T-cell depleted. T-cell–inflamed tumors were enriched in anti-inflammatory M2 macrophages and exhausted T cells and associated with shorter overall survival relative to T-cell–depleted tumors (HR, 2.62; <i>P</i> < 0.05). Among all prostate cancer types in the cohort, NEPC was identified to be the most immune depleted, wherein only 9 out of the 36 total NEPC tumors were classified as T-cell inflamed. These inflamed NEPC cases were enriched in IFN gamma signaling and <i>PD-1</i> signaling compared with other NEPC tumors. Comparison of NEPC with SCLC revealed that NEPC had poor immune content and less mutations compared with SCLC, but expression of checkpoint genes <i>PD-L1</i> and <i>CTLA-4</i> was comparable between NEPC and SCLC.</p>Conclusions:<p>NEPC is characterized by a relatively immune-depleted tumor immune microenvironment compared with other primary and metastatic prostate adenocarcinoma except in a minority of cases. These findings may inform development of immunotherapy strategies for patients with advanced prostate cancer.</p></div>