title: Pretreatment frequency of circulating IL-17+ CD4+ T-cells, but not Tregs, correlates with clinical response to whole-cell vaccination in prostate cancer patients.
abstract: The aim of this study was to determine the prognostic implications of the pretreatment level of Th17 cells compared with regulatory T-cell status in prostate cancer patients receiving active whole cell immunotherapy. Ten-color flow cytometry was used to analyze IL-17-producing CD4(+) T-cells in the peripheral blood of hormone-resistant non-bone metastatic prostate cancer patients prior to immunotherapy with an allogeneic whole-cell vaccine. Surface expression of the chemokine receptors CCR4 and CCR6 was used to further subdivide IL-17-producing cells into subsets with distinct homing properties. The frequency of circulating regulatory T-cells (Tregs), defined as CD3(+)CD4(+)CD127(lo)Foxp3(+)CD25(+) was compared in the same patients. The frequency of CCR4(-)IL-17(+)CD4(+) T-cells prevaccination inversely correlated with time to disease progression (TTP) in 23 prostate cancer patients. Furthermore, responder (R) patients with statistically significant reductions in PSA velocity (PSAV) in response to the immunotherapy (n = 9), showed a Th17 profile similar to healthy male controls and significantly different from non-responder (NR) patients (n = 14) (i.e., those without any significant reduction in PSAV). In contrast, the frequency of Tregs in peripheral blood in PSA-R (n = 11) and -NR (n = 14) patients was similar (but in both cases, significantly higher than in age-matched healthy men). Accordingly, there was no significant correlation between frequency of Tregs and TTP in these late-stage prostate cancer patients undergoing active immunotherapy. These data imply an important role for IL-17-producing helper T-cells in cancer immunology and highlight their potential use as a pretreatment screen to ensure appropriate treatment is offered to hormone-resistant prostate cancer patients.
authors.affiliation: Department of Internal Medicine II, Center for Medical Research, University of Tübingen, Tübingen, Germany. evelyna.derhovanessian@klinikum.uni-tuebingen.de
authors.forename: Evelyna
authors.initials: E
authors.lastname: Derhovanessian
authors.forename: Victoria
authors.initials: V
authors.lastname: Adams
authors.forename: Karin
authors.initials: K
authors.lastname: Hähnel
authors.forename: Andrea
authors.initials: A
authors.lastname: Groeger
authors.forename: Hardev
authors.initials: H
authors.lastname: Pandha
authors.forename: Stephen
authors.initials: S
authors.lastname: Ward
authors.forename: Graham
authors.initials: G
authors.lastname: Pawelec
mesh_terms: D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D005434:Flow Cytometry; D006801:Humans; D007167:Immunotherapy; D020381:Interleukin-17 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009376:Neoplasms, Hormone-Dependent / Q000276:immunology / Q000473:pathology / Q000628:therapy; D011467:Prostate / Q000276:immunology / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D020381:Interleukin-17