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-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.

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 involvement) 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 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.

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.

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Acknowledgements

To the involved institution(s), the patients and those that provided and cared for study patients.

Funding

Reis LO: CAPES, Brazil—Grant: BEX 14679/13-2 and CNPq Research Productivity, Brazil—Grant: 302622/2015-2

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Affiliations

Authors

Contributions

MAC: clinical data collection, data analysis, and manuscript editing; KLF and ACM: experimental data collection and analysis, and manuscript writing; CRM: funding acquisition, manuscript editing and supervision. LOR: project development, funding acquisition, manuscript writing, and supervision.

Corresponding author

Correspondence to Leonardo Oliveira Reis.

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Conflict of interest

None declared.

Research involving human participants

Research ethics committee approval protocol nº 2.013.568.

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Obtained from all patients.

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Leonardo Oliveira Reis: Preliminary results awarded Best Moderated Poster at 2018 American Urological Association Annual Meeting, May 18–21, San Francisco.

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Cerqueira, M.A., Ferrari, K.L., de Mattos, A.C. et al. T cells CD4+/CD8+ local immune modulation by prostate cancer hemi-cryoablation. World J Urol 38, 673–680 (2020). https://doi.org/10.1007/s00345-019-02861-0

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Keywords

  • Tumor-infiltrating T cells
  • Prostate cancer
  • Ablation
  • Tumor microenvironment