T cells CD4+/CD8+ local immune modulation by prostate cancer hemi-cryoablation.

Abstract

Tumors escape from the immune system by decreasing CD8+ and increasing CD4+ T cells' activity, druggable targets. Thermal ablation might activate tumor-specific T cells by raising the presentation of tumor-specific antigens and hindering tumor negative immune regulation. Our aim was to assess T cell infiltrate pre- and post-cryoablation in a prospective observational study. A total of 240 sextant prostate biopsies cores (12 cores/patient) were collected from 10 unilateral prostate cancer patients (T1c, PSA density < 0.15ng/dL, Gleason grade group 1, ≤ 2 cancer biopsy cores, and < 50% cancer core involvement) at diagnosis and 12months after hemi-cryoablation. Cancer-positive (Diag+) and cancer-negative (Diag-) lobes at diagnosis and the same areas 12months after hemi-cryoablation (Cryo+ and Cryo-, respectively) were explored by immunohistochemistry for infiltrating CD4+ and CD8+ T cells (in 45 random fields per prostate lobe, 400× magnification). The quantitative analysis of cells/mm2 and CD4+/CD8+ ratio were performed and compared among Diag+, Diag-, Cryo+, and Cryo- using ImageJ software. There was a significant increase in tumor-infiltrating CD8+ T cells/mm2 in the Cryo+ tissue (mean, SD 0.31, 0.30) compared to Diag+ (0.18, 0.15), p = 0.015; confirmed in prostate acini (hot spots), p = 0.029, in which infiltrating CD4+/CD8+ T cells' ratio decreased after hemi-cryoablation, p = 0.006. Infiltrating CD4+ T cells/mm2 presented a trend to decrease in Cryo+ (0.26, 0.27) compared to Diag+ (0.38, 0.32). This is the first study to show local immune modulation after prostate cancer cryoablation, characterized by decreasing CD4+/CD8+ T cells' ratio, potential for clinical impact by unleashing the T-cell response to cancer. Future studies are necessary to explore different energies and longer follow-up clinical endpoints.