ARTICLE ABSTRACTElucidating the cellular immune components underlying aggressive prostate cancer, especially among African American (AA) men who are disproportionately affected by this disease compared to Caucasian American (CA) men, will support more inclusive precision medicine treatment strategies. We aimed to evaluate which immune-related genes and cell types are differentially expressed in AA tumors and how immunobiology 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 clinico-pathologic 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 vs Tumor Infiltrating Lymphocytes (TILs) were found in men with high grade pathologies and in men who later developed metastases. Low ratios of Mast cells vs TILs were associated with worse BCR-free survival and metastasis-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.