Metronomic cyclophosphamide induces regulatory T cells depletion and PSA-specific T cells reactivation in patients with biochemical recurrent prostate cancer

Int J Cancer. 2020 Aug 15;147(4):1199-1205. doi: 10.1002/ijc.32803. Epub 2019 Dec 11.

Abstract

Biochemical recurrence (BCR) occurs in up to 40% of prostate cancer patients after prostatectomy. In our study, we performed an immune monitoring study in 20 prostate cancer patients with BCR previously treated with metronomic cyclophosphamide (mCTX). We observed a decrease of regulatory T cells (Tregs) from 2 months and this was more pronounced after 6 months of mCTX treatment. This drop of Tregs was associated with increased level of activated HLADR+ CD45R0+ T cells in peripheral blood. Furthermore, a reactivation of Th1 polarized anti-PSA T-cell response was detected in BCR patients treated with mCTX. However, dendritic cell subsets counts and activation were not influenced by the treatment. In the clinical setting, we found that PSA level control was observed in 82% (9/11) of patients with a significant diminution of Tregs after mCTX compared to 33% (3/9) in patients without Tregs decrease. In addition, 30% (6/20) of patients previously treated with mCTX remained free for androgen deprivation therapy. In conclusion, Tregs diminution and immune activation associated with PSA level control occurred after mCTX in prostate cancer patients with BCR.

Keywords: anti-PSA T-cell response; biochemical recurrence; metronomic cyclophosphamide; prostate cancer; regulatory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Metronomic
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Cyclophosphamide / administration & dosage*
  • Humans
  • Lymphocyte Activation / drug effects
  • Lymphocyte Depletion / methods
  • Male
  • Neoplasm Recurrence, Local
  • Prostate-Specific Antigen / metabolism*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / pathology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • Antineoplastic Agents, Alkylating
  • Cyclophosphamide
  • Prostate-Specific Antigen