Prevalence of tumour-infiltrating CD103+ cells identifies therapeutic-sensitive prostate cancer with poor clinical outcome

Abstract

Background: The clinical significance and immune correlation of CD103⁺ cells in prostate cancer (PCa) remain explored.

Methods: In total, 1080 patients with PCa underwent radical prostatectomy from three cohorts were enrolled for retrospective analysis. Tumour microarrays were constructed and fresh tumour samples were analysed by flow cytometry.

Results: High CD103⁺ cell infiltration correlated with reduced biochemical recurrence (BCR)-free survival in PCa. Adjuvant hormone therapy (HT) prolonged the BCR-free survival for high-risk node-negative diseases with CD103⁺ cell abundance. CD103⁺ cell infiltration correlated with less cytotoxic expression and increased infiltration of CD8⁺ and CD4⁺ T cells, M1 macrophages and mast cells in PCa. Intratumoral CD8⁺ T cell was the predominant source of CD103, and the CD103⁺ subset of CD8⁺ T cells was featured with high IL-10, PD-1 and CTLA-4 expression. Tumour-infiltrating CD103⁺ CD8⁺ T cells exerted anti-tumour function when treated with HT ex vivo.

Discussion: CD103⁺ cell infiltration predicted BCR-free survival and response to adjuvant HT in PCa. CD103⁺ cell infiltration correlated with an enriched but immune-evasive immune landscape. The study supported a model that CD103 expression conferred negative prognostic impact and immunosuppressive function to tumour-infiltrating CD8⁺ T cells, while the CD103⁺ CD8⁺ T cells exhibited a powerful anti-tumour immunity with response to HT.