T CELLS CD4+/CD8+ LOCAL IMMUNE MODULATION BY PROSTATE CANCER HEMI-CRYOABLATION
Purpose: Tumors escape from the immune system by decreasing CD8+ and increasing CD4+ T cells activity, drug able 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.
Methods: Total of 120 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 involvement) at diagnosis and 12 months after hemi-cryoablation. Cancer positive (Diag+) and negative (Diag-) lobes at diagnosis and the same areas 12 months 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, x400 magnification). The quantitative analysis of cells/mm2 and CD4+/CD8+ ratio were performed and compared among Diag+, Diag-, Cryo+, Cryo- using ImageJ software.
Results: 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).
Conclusions: 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.
tumor-infiltrating T cells; prostate cance;, ablation; tumor microenvironment
Unicamp - Sao Paulo - Brasil
Leonardo O Reis, Michel A Cerqueira, Karen L Ferrari, Carlos R Monti