Single cell profiling of peripheral blood mononuclear cells in diverse men with prostate cancer reveals a fatal disease-associated immune signature - Capsule Feb 10, 2026

Le résumé fourni par la source

Alterations in peripheral immunity may contribute to fatal prostate cancer and the excessive disease burden among African American (AA) men. Thus, we investigated peripheral immunity in prostate cancer patients in association with disease outcome and AA identity. We performed single cell RNA and T cell receptor (TCR) sequencing using peripheral blood mononuclear cells (PBMC) from a diverse cohort of 43 prostate cancer patients with survival follow-up and 16 healthy controls. Analyzing 273,229 high-quality PBMC, we observed that men who developed fatal prostate cancer distinctively express the LAG3 and TIGIT exhaustion markers in their CD8⁺ T effector memory cells (CD8 TEM) and have a reduced CD4/CD8 ratio, an indicator of immunosenescence. These men also showed a loss of type-2 conventional dendritic cells (cDC2). Further analyses revealed additional functional differences in cDC2, CD16+ monocytes, and CD8 TEM comparing men with and without fatal disease. In cDC2, the anabolism, inflammatory, interferon, and androgen responses, and TNFα-signaling-via-NFκB were down-regulated in association with disease fatality. Comparing AA with European American patients, we noticed an interferon signature and upregulated LAG3 and TIGIT in AA PBMC. For cDC2 and CD16+ monocytes, fatal disease and AA patients showed shared marker expression. Furthermore, TCR profiling discovered over-representation of large, hyperexpanded clonotypes and a lower TCR diversity among fatal disease and AA patients. Lastly, the CD8 TEM functional status emerged as a candidate predictor of disease fatality. We conclude that peripheral immunity may distinctly vary in association with disease outcome and ancestry of prostate cancer patients.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.