Spatially organized lymphocytic microenvironments in high grade primary prostate tumors

The spatial organization and composition of the tumor-immune microenvironment (TME) play a critical role in shaping the progression of many solid cancers, but the organization of the TME in primary prostate cancer (PCa) remains poorly characterized. We therefore profiled the abundance and spatial distributions of major cell types involved in adaptive immunity in 29 radical prostatectomy specimens stratified into high (HGG; n=14) and low Gleason-grade (LGG; n=15). Compared to LGG, HGG PCa exhibited significantly greater B and T cell infiltration with many immune cells organized into clusters, some of which resembled tertiary lymphoid structures (TLSs). In HGG tumors, these clusters were dense, symmetric, rich in PD-1⁺ T cells, and frequently proximate to the tumor compartment. LGG clusters were less well organized, and T cell depleted. Thus, a subset of high-grade PCa harbor organized immune clusters that may play a role in tumor control and contain therapeutically targetable T and B cells.