Cancer Immunology, Immunotherapy

, Volume 60, Issue 2, pp 197–206 | Cite as

Analysis of circulating regulatory T cells in patients with metastatic prostate cancer pre- versus post-vaccination

  • Matteo Vergati
  • Vittore Cereda
  • Ravi A. Madan
  • James L. Gulley
  • Ngar-Yee Huen
  • Connie J. Rogers
  • Kenneth W. Hance
  • Philip M. Arlen
  • Jeffrey Schlom
  • Kwong Y. Tsang
Original Article

Abstract

We have previously shown that the suppressive function of regulatory T cells (Tregs) from peripheral blood mononuclear cells (PBMCs) is enhanced in patients with prostate cancer when compared with healthy individuals. Two phase II studies using the PSA-TRICOM vaccine in patients with metastatic castration-resistant prostate cancer (mCRPC) showed evidence of patient benefit in terms of enhanced survival. The Halabi nomogram has been used to predict survival (HPS) of patients with mCRPC treated with conventional chemotherapy or second-line hormonal therapy. Tregs from PBMCs of patients (n = 23) with mCRPC were obtained pre- and post-three monthly vaccinations, and analyzed for number, phenotype, and suppressive function. Changes post- versus pre-vaccination in these parameters were compared with 3-year survival and HPS. No differences in Treg numbers were observed post- versus pre-vaccination. Trends (P = 0.029) were observed between overall survival (OS) and a decrease in Treg suppressive function post- versus pre-vaccination. Trends were also observed in analyzing effector:Treg (CD4+CD25+CD127FoxP3+CTLA4+) ratio post- versus pre-vaccination with OS versus HPS. These data provide preliminary evidence for a possible association between improved OS and a decrease in Treg function when PBMCs are analyzed after three monthly vaccinations. Patients with an OS > HPS were more likely to have decreased Treg function following vaccine. Larger studies to confirm and extend these findings are warranted.

Keywords

Cancer vaccine Prostate cancer Immunotherapy Regulatory T cells Vaccination 

Notes

Acknowledgments

The authors thank Bonnie L. Casey and Debra Weingarten for their editorial assistance in the preparation of this manuscript. Intramural research program of the Center for Cancer Research, National Cancer Institute, NIH.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© US Government 2010

Authors and Affiliations

  • Matteo Vergati
    • 1
  • Vittore Cereda
    • 1
  • Ravi A. Madan
    • 1
    • 2
  • James L. Gulley
    • 1
    • 2
  • Ngar-Yee Huen
    • 1
  • Connie J. Rogers
    • 1
  • Kenneth W. Hance
    • 1
  • Philip M. Arlen
    • 1
    • 2
  • Jeffrey Schlom
    • 1
  • Kwong Y. Tsang
    • 1
  1. 1.Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer InstituteNational Institutes of HealthBethesdaUSA
  2. 2.Medical Oncology Branch, Center for Cancer Research, National Cancer InstituteNational Institutes of HealthBethesdaUSA

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