Prognostic significance of tumor immune microenvironment dynamics in prostate cancer induced by androgen deprivation therapy.
Abstract
398 Background: The dynamics of the prostate cancer microenvironment through androgen regulation are unclear. In this study, we analyzed the relationship between the dynamics of the immune microenvironment and prognosis after androgen deprivation therapy. Methods: We retrospectively reviewed the patients who underwent radical prostatectomy at our institution. Among them, 104 patients received prostate needle biopsy and neoadjuvant androgen deprivation therapy at the same institution. These cases were compared before and after androgen deprivation therapy. Immune cell infiltration in the cancer areas was assessed using multiplex fluorescent immunohistochemistry. Transcriptome analysis and gene panel analysis by next-generation sequencing were used to systematically and comprehensively analyze the expression and mechanisms of the immune microenvironment. Results: Few immune cells were detected in the needle biopsies before androgen deprivation therapy. After androgen deprivation therapy, prostatectomy specimens showed a significant change in various immune cells, including CD4 + T cells, CD8 + T cells, Foxp3 + regulatory T cells, CD204 + macrophages, and CD20 + B cells (P< 0.001). In particular, CD8 + T cells and CD20 + B cells were significantly increased compared to patients who did not receive androgen deprivation therapy followed by total prostatectomy (P<0.001). Clustering analysis allowed stratification into three groups: One group had a predominant increase in CD8 + T cells after androgen deprivation therapy, another group had a predominant increase in CD20 + B cells, and the third group had no significant increase. The group with increased CD8 + T cells had a significantly higher 5-year biochemical recurrence rate of 56 % (P=0.045). Differences in the mechanisms of androgen metabolism were observed among these cases. Conclusions: Differences in immune induction after androgen deprivation therapy have an impact on the prognosis of prostate cancer.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (11)
Yoshinori Yanai
Department of Urology, Keio University School of Medicine, Tokyo, Japan
Takeo Kosaka
Department of Urology, Keio University School of Medicine, Tokyo, Japan
Shuji Mikami
Masashi Arai
Department of Urology, Keio University School of Medicine, Tokyo, Japan
Yuto Baba
Keitaro Watanabe
Department of Urology, Keio University School of Medicine, Tokyo, Japan
Toshikazu Takeda
Department of Urology, Keio University School of Medicine, Tokyo, Japan
Kazuhiro Matsumoto
Makiko Yamashita
Department of Advanced Medical Development, The Cancer Institute Hospital of Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan
Shigehisa Kitano
Department of Advanced Medical Development, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo
Mototsugu Oya