Immunologic Assessment of Tumors from a Race-matched Military Cohort Identifies Mast Cell Depletion as a Marker of Prostate Cancer Progression

Elucidating the cellular immune components underlying aggressive prostate cancer, especially among African American (AA) men who are disproportionately affected by this disease comparedwithCaucasianAmerican (CA) men, will support more inclusive precision medicine treatment strategies. We aimed to evaluatewhich immune-related genes and cell types are differentially expressed inAAtumors and howimmunobiology impacts prostate cancer progression. We purified nucleic acid from tumor biopsies, obtained following radical prostatectomy, from 51 patients (AA = 26, CA = 25). Gene expression was measured using the NanoString platform from which we estimated immune cell abundances and assessed differences between groups based on clinicopathologic data. Product-limit estimates determined associations with biochemical recurrence (BCR)-free and metastasis-free survival. DVL2 and KLRC2 were significantly upregulated in CA tumors and were also associated with worse disease progression. No significant differences in immune cell abundances by race were observed. Highly significant reductions in abundances of mast cells versus tumor-infiltrating lymphocytes (TIL) were found inmen with high-grade pathologies and inmen who later developed metastases. Low ratios of mast cells versus TILs were associated withworse BCR-free survival andmetastasis-free survival. Although estimated immune cell abundances were not different by race, we identified genes involved in metabolism and natural killer cell functions that were differentially expressed between AA and CA tumors. Among the entire cohort, depletion of mast cells within prostatectomy tumors was characteristic of advanced disease and susceptibility to disease progression. Significance: Our findings demonstrate that there are immune-related genes and pathways that differ by race. Impaired intratumoral cellular immune composition, especially for TIL-normalized mast cells, may be vital in predicting and contributing to prostate cancer disease progression.