Analysis of circulating regulatory T cells in patients with metastatic prostate cancer pre- versus post-vaccination.
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(+)CD127(-)FoxP3(+)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.
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
Matteo
M
Vergati
Vittore
V
Cereda
Ravi A
RA
Madan
James L
JL
Gulley
Ngar-Yee
NY
Huen
Connie J
CJ
Rogers
Kenneth W
KW
Hance
Philip M
PM
Arlen
Jeffrey
J
Schlom
Kwong Y
KY
Tsang
D015703:Antigens, CD / Q000378:metabolism; D060908:CTLA-4 Antigen; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D009362:Neoplasm Metastasis / Q000276:immunology; D011471:Prostatic Neoplasms / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D019496:Cancer Vaccines