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

Abstract

Purpose Tumors escape from the immune system by decreasing CD8+ and increasing CD4+ T cells’ activity, druggable targets. Thermal ablation might activate tumor-specifc T cells by raising the presentation of tumor-specifc antigens and hindering tumor negative immune regulation. Our aim was to assess T cell infltrate pre- and post-cryoablation in a prospec tive observational study. Methods A total of 240 sextant prostate biopsies cores (12 cores/patient) were collected from 10 unilateral prostate cancer patients (T1c, PSA density <0.15 ng/dL, Gleason grade group 1, ≤2 cancer biopsy cores, and <50% cancer core involve ment) at diagnosis and 12 months after hemi-cryoablation. Cancer-positive (Diag+) and cancer-negative (Diag−) lobes at diagnosis and the same areas 12 months after hemi-cryoablation (Cryo+ and Cryo−, respectively) were explored by immu nohistochemistry for infltrating CD4+ and CD8+ T cells (in 45 random felds per prostate lobe, 400× magnifcation). The quantitative analysis of cells/mm2 and CD4+/CD8+ ratio were performed and compared among Diag+, Diag−, Cryo+, and Cryo− using ImageJ software. Results There was a signifcant increase in tumor-infltrating CD8+ T cells/mm2 in the Cryo+ tissue (mean, SD 0.31, 0.30) compared to Diag+ (0.18, 0.15), p=0.015; confrmed in prostate acini (hot spots), p=0.029, in which infltrating CD4+/ CD8+ T cells’ ratio decreased after hemi-cryoablation, p=0.006. Infltrating CD4+ T cells/mm2 presented a trend to decrease in Cryo+ (0.26, 0.27) compared to Diag+ (0.38, 0.32). Conclusions This is the frst 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 stud ies are necessary to explore diferent energies and longer follow-up clinical endpoints