Immune cell single-cell RNA sequencing analyses link an age-associated T cell subset to symptomatic benign prostatic hyperplasia

Meaghan Broman¹Nadia Marie Atallah¹Renee Vickman²Greg Cresswell³Harish Kothandaraman¹Andree Kolliegbo¹Juan Sebastian Paez Paez⁴Alexander Glaser^2,5Brian Helfand^2,5Gervaise Henry⁶Douglas Strand⁷Omar Franco⁸Simon Hayward²Timothy Ratliff^1*

• ¹Purdue University, West Lafayette, United States
• ²NorthShore University HealthSystem, Evanston, Illinois, United States
• ³George Washington University, Washington, D.C., District of Columbia, United States
• ⁴Talus Bio, Seattle, United States
• ⁵Pritzker School of Medicine, The University of Chicago, Chicago, Illinois, United States
• ⁶DNAnexus, Inc., Mountain View, California, United States
• ⁷Urology Department, University of Texas Southwestern, Dallas, United States
• ⁸Louisiana State University in Shreveport, Shreveport, Louisiana, United States

Benign prostatic hyperplasia (BPH) is among the most common age-associated diseases in men; however, the contribution of age-related changes in immune cells to BPH is not clear. The current study determined that an age-associated CD8 + T cell subset (Taa) with high Granzyme K (GZMK hi ) and low Granzyme B (GZMB low ) gene expression infiltrate aged human prostates and positively correlate with International Prostate Symptom Score (IPSS). A velocity analysis indicated that CD8 + T cell differentiation is altered in large BPH prostates compared to small age-matched prostates, favoring Taa accumulation. In vitro granzyme K treatment of human BPH patient-derived large prostate fibroblasts increased secretion of proinflammatory senescence-associated secretory phenotype (SASP)-associated cytokines. These data suggest that granzyme K-mediated stimulation of prostate stromal fibroblast SASP cytokine and chemokine production promotes prostate immune cell recruitment and activation. Overall, these results connect symptomatic BPH with immune aging.