Introduction & Objective:
Regulatory T cells (Treg) play important roles in suppression of the immune response, including anti-tumor immunity. C-C chemokine receptor 4 (CCR4) is highly expressed on effector Tregs, and the anti-CCR4 antibody is attracting attention as a novel immunotherapeutic agent for solid tumors. The purpose of this study was to evaluate the expression of CCR4-positive Tregs in biopsy specimens of men with prostate cancer with a poor prognosis and to estimate the clinical potential of CCR4-targeting therapy for prostate cancer.
Material & Methods:
Data for 60 men diagnosed with prostate cancer based on transrectal 12-core systemic biopsy were retrospectively analyzed. They were divided into two groups, a good prognosis group comprising men with no disease progression during the observation period and a poor prognosis group comprising men with progression to castration resistant prostate cancer. In the biopsy cores, the core with the highest tumor volume was selected for immunohistochemical evaluation. Tregs were evaluated using immunohistochemistry with double staining using anti-forkhead box protein 3 (FOXP3) antibodies and anti-CCR4 antibodies. The number of CCR4+/- FOXP3+ cells in the biopsy specimens were compared between the two groups. Furthermore, the correlation between the number of CCR4+ FOXP3+ cells and clinical stage, PSA at diagnosis, and Gleason score were evaluated.
The good prognosis group included 29 men and the poor prognosis group included 31 men. Approximately 70-80% of FOXP3+ cells were positive for CCR4. There was no significant difference in the ratio of number of CCR4+ FOXP3+ cells to the number of total FOXP3+ cells between the poor and good prognosis groups. However, the total number of FOXP3+ cells significantly increased in the poor prognosis group than in the good prognosis group (200.1 ± 174.8 vs. 38.1 ± 38.1, p < 0.01). Furthermore, the number of CCR4+ FOXP3+ cells significantly increased in the poor prognosis group than in the good prognosis group (123.6 ± 99.1 vs. 58.88 ± 26.4, p < 0.01). The number of CCR4+ FOXP3+ cells positively correlated with clinical stage (ρ = 0.558, p < 0.001) and Gleason score (ρ = 0.458, p = 0.006) in prostate cancer. However, there was no significant correlation between the number of CCR4+ FOXP3+ cells and PSA at diagnosis. The men with a lower number of CCR4+ FOXP3+ cells had a significantly longer median survival time than those with high expression (not reached vs. 69.0 months; p = 0.040).
Our results suggest the clinical potential of CCR4-targeted therapy for poor prognosis prostate cancer.
Citation Format: Masahito Watanabe, Kent Kanao, Susumu Suzuki, Hiroyuki Muramatsu, Shingo Morinaga, Keishi Kajikawa, Ikuo Kobayashi, Genya Nishikawa, Yoshiharu Kato, Kogenta Nakamura, Kazuhiro Yoshikawa, Ryuzo Ueda, Makoto Sumitomo. Increased CCR4-positive regulatory T cells in biopsy specimen of poor prognosis prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3961. doi:10.1158/1538-7445.AM2017-3961