TY - JOUR
T1 - Increased infiltration of CCR4-positive regulatory T cells in prostate cancer tissue is associated with a poor prognosis
AU - Watanabe, Masahito
AU - Kanao, Kent
AU - Suzuki, Susumu
AU - Muramatsu, Hiroyuki
AU - Morinaga, Singo
AU - Kajikawa, Keishi
AU - Kobayashi, Ikuo
AU - Nishikawa, Genya
AU - Kato, Yoshiharu
AU - Zannami, Kenji
AU - Nakamura, Kogenta
AU - Tsuzuki, Toyonori
AU - Yoshikawa, Kazuhiro
AU - Ueda, Ryuzo
AU - Sumitomo, Makoto
N1 - Funding Information:
This work was supported by JSPS KAKENHI Grant Number JP18K16715f, C18K07277 and JP18K07210, and resarch grant from Aichi Medical University. RU had grant from Kyowa Hakko Kirin Co Ltd, grant from Chugai Pharmaceutial Co Ltd, grant from Medical & Biological Laboratories Co Ltd, grant from Rikaken Co Ltd, grant fromOno Pharmaceutial Co Ltd.
Funding Information:
This work was supported by JSPS KAKENHI Grant Number JP18K16715f, C18K07277 and JP18K07210, and resarch grant from Aichi Medical University. RU had grant from Kyowa Hakko Kirin Co Ltd, grant from Chugai Pharmaceutial Co Ltd, grant from Medical & Biological Laboratories Co Ltd, grant from Rikaken Co Ltd, grant fromOno Pharmaceutial Co Ltd.
Publisher Copyright:
© 2019 Wiley Periodicals, Inc.
PY - 2019/10
Y1 - 2019/10
N2 - Background: Regulatory T cells (Tregs) play important roles in the suppression of immune responses, including antitumor immune responses. C-C chemokine receptor 4 (CCR4) is highly expressed on effector Tregs, and anti-CCR4 antibody is attracting attention as a novel immunotherapeutic agent for solid tumors. This study aimed to evaluate the expression of CCR4-positive Tregs (CCR4+Tregs) in prostate cancer and estimate the clinical potential of CCR4-targeting therapy for prostate cancer. Methods: A total of 15 radical prostatectomy (RP) specimens and 60 biopsy specimens from individuals diagnosed with prostate cancer were analyzed to evaluate the infiltration of CCR4+Tregs in prostate cancer. The relationships between the number of CCR4+Tregs and clinical parameters were investigated in RP and biopsy specimens. Moreover, the total number of Tregs, CCR4+Tregs, and T cells and the ratio of CCR4+Tregs to Tregs and T cells in biopsy specimens were compared between patients with poor prognosis who progressed to castration-resistant prostate cancer (CRPC) within 12 months (n = 13) and those with good prognosis who were stable with hormone-sensitive prostate cancer over 12 months (n = 47). Furthermore, biopsy specimens were divided into two groups: low and high CCR4+Treg expression groups and the prognosis was compared between them. Results: There was a higher expression of CCR4+Tregs in RP specimens with a higher (≥8) Gleason score than in those with a lower (<8) Gleason score (P =.041). In biopsy specimens, 65.9% Tregs were positive for CCR4. The number of CCR4+Tregs positively correlated with clinical stage (P <.001) and Gleason score (P =.006). The total number of Tregs and CCR4+Tregs significantly increased in the poor prognosis group compared with that in the good prognosis group (P =.024 and.01, respectively). Furthermore, patients with lower CCR4+Treg expression levels showed a significantly longer time to progression to CRPC (not reached vs 27.3 months; P <.001) and median survival time (not reached vs 69.0 months; P =.014) than those with higher expression levels. Conclusions: CCR4+Tregs are highly infiltrated in the prostate tissue of patients with poor prognosis with potential to progress to CRPC. Furthermore, the degree of infiltration of CCR4+Tregs is related to the prognosis of prostate cancer.
AB - Background: Regulatory T cells (Tregs) play important roles in the suppression of immune responses, including antitumor immune responses. C-C chemokine receptor 4 (CCR4) is highly expressed on effector Tregs, and anti-CCR4 antibody is attracting attention as a novel immunotherapeutic agent for solid tumors. This study aimed to evaluate the expression of CCR4-positive Tregs (CCR4+Tregs) in prostate cancer and estimate the clinical potential of CCR4-targeting therapy for prostate cancer. Methods: A total of 15 radical prostatectomy (RP) specimens and 60 biopsy specimens from individuals diagnosed with prostate cancer were analyzed to evaluate the infiltration of CCR4+Tregs in prostate cancer. The relationships between the number of CCR4+Tregs and clinical parameters were investigated in RP and biopsy specimens. Moreover, the total number of Tregs, CCR4+Tregs, and T cells and the ratio of CCR4+Tregs to Tregs and T cells in biopsy specimens were compared between patients with poor prognosis who progressed to castration-resistant prostate cancer (CRPC) within 12 months (n = 13) and those with good prognosis who were stable with hormone-sensitive prostate cancer over 12 months (n = 47). Furthermore, biopsy specimens were divided into two groups: low and high CCR4+Treg expression groups and the prognosis was compared between them. Results: There was a higher expression of CCR4+Tregs in RP specimens with a higher (≥8) Gleason score than in those with a lower (<8) Gleason score (P =.041). In biopsy specimens, 65.9% Tregs were positive for CCR4. The number of CCR4+Tregs positively correlated with clinical stage (P <.001) and Gleason score (P =.006). The total number of Tregs and CCR4+Tregs significantly increased in the poor prognosis group compared with that in the good prognosis group (P =.024 and.01, respectively). Furthermore, patients with lower CCR4+Treg expression levels showed a significantly longer time to progression to CRPC (not reached vs 27.3 months; P <.001) and median survival time (not reached vs 69.0 months; P =.014) than those with higher expression levels. Conclusions: CCR4+Tregs are highly infiltrated in the prostate tissue of patients with poor prognosis with potential to progress to CRPC. Furthermore, the degree of infiltration of CCR4+Tregs is related to the prognosis of prostate cancer.
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U2 - 10.1002/pros.23890
DO - 10.1002/pros.23890
M3 - Article
C2 - 31390096
AN - SCOPUS:85070496898
SN - 0270-4137
VL - 79
SP - 1658
EP - 1665
JO - Prostate
JF - Prostate
IS - 14
ER -