Spatially organized lymphocytic microenvironments in high grade primary prostate tumors
Ali Amiryousefi1,2, Jeremiah Wala3, Jia-Ren Lin1,2
1Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Biorxiv : the Preprint Server for Biology
|September 26, 2025
Summary
High-grade prostate cancer (PCa) shows increased B and T cell infiltration, forming organized immune clusters resembling tertiary lymphoid structures (TLSs). These structures may aid tumor control and offer therapeutic targets in advanced PCa.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- The tumor-immune microenvironment (TME) influences cancer progression.
- The TME organization in primary prostate cancer (PCa) is not well understood.
Purpose of the Study:
- To investigate the spatial organization and composition of immune cells in high-grade versus low-grade PCa.
- To characterize the TME in primary prostate cancer.
Main Methods:
- Profiling of immune cell abundance and spatial distribution in 29 radical prostatectomy specimens.
- Stratification of specimens into high Gleason-grade (HGG) and low Gleason-grade (LGG) PCa.
Main Results:
- HGG PCa displayed significantly higher B and T cell infiltration compared to LGG PCa.
- Immune cells in HGG tumors formed organized clusters, some resembling tertiary lymphoid structures (TLSs).
- These HGG clusters were dense, rich in PD-1+ T cells, and located near the tumor, unlike less organized LGG clusters.
Conclusions:
- A subset of high-grade PCa features organized immune clusters potentially involved in tumor control.
- These immune clusters contain therapeutically targetable T and B cells, suggesting potential for novel PCa treatments.
