Abstract
Black men die more often of prostate cancer yet, interestingly, may derive greater survival benefits from immune-based treatment with sipuleucel-T. Since no signatures of immune-responsiveness exist for prostate cancer, we explored race-based immune-profiles to identify vulnerabilities. Here we show in multiple independent cohorts comprised of over 1,300 patient samples annotated with either self-identified race or genetic ancestry, prostate tumors from Black men or men of African ancestry have increases in plasma cell infiltrate and augmented markers of NK cell activity and IgG expression. These findings are associated with improved recurrence-free survival following surgery and nominate plasma cells as drivers of prostate cancer immune-responsiveness.
Highlights
Black men die more often of prostate cancer yet, interestingly, may derive greater survival benefits from immune-based treatment with sipuleucel-T
Similar trends were noticed in two additional cohorts: 1) The Cancer Genome Atlas (TCGA) which was annotated with genetic ancestry[8] (PC-B = 58; Prostate cancer (PC)-W = 410; Odds ratio=1.50, P = 0.057) and 2) a retrospective cohort of prostate tumors with whole transcriptomic data from radical prostatectomy at Durham Veterans Affairs Hospital (DVA) which was annotated with self-identified race (PC-B = 302; PCW = 236; Odds ratio=1.39, P = 0.014; Supplementary Tables 2– 3)
For men with PC receiving immunotherapy in the form of sipuleucel-T, treatment response correlates with induced elevated serum levels of anti-tumor IgG and, interestingly, longer survival was noted in self-identified Black men[4,32]
Summary
Black men die more often of prostate cancer yet, interestingly, may derive greater survival benefits from immune-based treatment with sipuleucel-T. We show in multiple independent cohorts comprised of over 1,300 patient samples annotated with either self-identified race or genetic ancestry, prostate tumors from Black men or men of African ancestry have increases in plasma cell infiltrate and augmented markers of NK cell activity and IgG expression. These findings are associated with improved recurrence-free survival following surgery and nominate plasma cells as drivers of prostate cancer immune-responsiveness. These findings suggest that plasma cells could be potential biomarkers or targets for therapeutic response to immunotherapy for use in future prospective evaluation
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