Abstract 4697: Immune cell infiltration and its clinical correlations in paired castration-naive and castration-resistant prostate cancers

Abstract

Abstract Ineffectiveness of immune checkpoint inhibitors in patients with castration- resistant prostate cancer (CRPC) suggests that CRPC may harbor a profound immunosuppressive tumor microenvironment. However, immune tumor microenvironment of CRPC has never been well investigated due to limited availability of castration-resistant tumor tissue. To characterize the changes in immune tumor microenvironment during CRPC progression and identify disease stage which is potentially favorable for immunotherapy, we studied the densities of tumor-infiltrating immune cells by using the immunohistochemical method and manual counting in paired castration-naive (CN) and castration-resistant (CR) tumors. We identified 11 metastatic prostate cancer patients who had received palliative transurethral resection of prostate both before androgen deprivation therapy (ADT) and at the time when castration resistance emerged from the hospital database during 2006.1~2017.3. We also used prostatic tissue from 5 patients with benign prostate hyperplasia as the normal prostate control. The median age at diagnosis of PC patients was 74.7 (range: 62-85) year-old. The numbers of tumors with Gleason score 7, 8, 9 and 10 were 1, 1, 6, and 2, respectively. The median PSA level at diagnosis was 96.6 (range: 3.3-847.7) ng/ml. The median overall survival after initiation of ADT was 48.8 months. The median density of CD4+ T cells (no./mm2) was 182.3 (45.0-363.5) for normal prostate, 160.9 (range: 12.6-240.6) for CNPC and 69.4 (range: 31-499.6) for CRPC (non-statistically significant; n.s.). The median density of CD8+ T cells (no./mm2) was 12.5 (range: 32.5-220.7) for normal prostate, 65.7 (range: 3.7-195.6) for CNPC and 53.8 (range: 4.4-190.4) for CRPC (n.s.). The median density of CD20+ B cells (no./mm2) was 132.1 (range: 54.6-514.4) for normal prostate, 112.2 (range: 3.7-298.9) for CNPC and 47.6 (range: 7.0-137.3) for CRPC (n.s.). The median density of CD68+ macrophages (no./mm2) was 31 (range: 0.4-248.7) for normal prostate, 77.5 (range: 3.7-403.7) for CNPC and 31.7 (range: 2.2-180.8) for CRPC (n.s.). The tumor-infiltrating immune cell densities in CNPC did not correlate with PSA level, Gleason score or ADT response. Only high B cell density in CNPC was prognostic for overall survival (median: 23.9 months for patients with high tumor-infiltrating B cell density vs. 64 months for patients with low tumor-infiltrating B cell density; P=0.0463). In conclusion, immune tumor microenvironment of CNPC and CRPC is very similar and is not different from normal prostate. It suggests that immune checkpoint inhibitors may not be effective against CNPC unless combining with other treatment, such as ADT or radiotherapy, which can reprogram the tumor microenvironment toward more immunosupportive. Citation Format: Ying-Chun Shen, Chia-Tung Shun, Ching-Ping Yeh, Jhe-Cyuang Kuo, Yu-Chieh Tsai, Chung-Hsin Chen, Chao-Yuan Huang, Yeong-Shiau Pu. Immune cell infiltration and its clinical correlations in paired castration-naive and castration-resistant prostate cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4697.