B7 score and T cell infiltration stratify immune status in prostate cancer

作者：Qianghua Zhou, Kaiwen Li, Yiming Lai, Kai Yao, Qiong Wang, Xiangyu Zhan, Shirong Peng, Wenli Cai, Wei Yao, Xingxing Zang, Kewei Xu, Jian Huang, Hai Huang · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2021 · DOI：10.1136/jitc-2021-002455 · 被引用次数：38 · 研究领域：Cancer Immunotherapy and Biomarkers、Immunotherapy and Immune Responses、Cancer, Stress, Anesthesia, and Immune Response

Background Although immune checkpoint inhibitors (ICIs), especially programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) axis blockers, exhibit prominent antitumor effects against numerous malignancies, their benefit for patients with prostate cancer (PCa) has been somewhat marginal. This study aimed to assess the feasibility of B7-H3 or HHLA2 as alternative immunotherapeutic targets in PCa. Methods Immunohistochemistry was performed to evaluate the expression pattern of PD-L1, B7-H3 and HHLA2 and the infiltration of CD8 + and Foxp3 + lymphocytes in 239 PCa tissues from two independent cohorts. The correlations between B7-H3 and HHLA2 and clinicopathological features, including the presence of CD8 + and Foxp3 + tumor-infiltrating lymphocytes (TILs), were explored. Results HHLA2 expression was much higher than PD-L1 expression but lower than B7-H3 expression in PCa tissues. High expression of both B7-H3 and HHLA2 was significantly associated with higher Gleason score and tumor stage, lymph node metastasis and dismal overall survival (OS) and cancer-specific survival (CSS). Moreover, a high B7 score, defined as high B7-H3 expression and/or high HHLA2 expression, was an independent prognostic predictor for PCa. Of note, a high B7 score was negatively correlated with CD8 + TILs. Importantly, a new immune classification, based on the B7 score and CD8 + TILs, successfully stratified OS and CSS in PCa. Conclusions Both B7-H3 and HHLA2 have a critical impact on th...