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

• Published in: Journal for immunotherapy of cancer Vol. 9; no. 8; p. e002455
• Main Authors: Zhou, Qianghua, Li, Kaiwen, Lai, Yiming, Yao, Kai, Wang, Qiong, Zhan, Xiangyu, Peng, Shirong, Cai, Wenli, Yao, Wei, Zang, Xingxing, Xu, Kewei, Huang, Jian, Huang, Hai
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.08.2021; BMJ Publishing Group
• Series: Original research
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - metabolism; Cancer; Cancer therapies; Humans; Immune checkpoint inhibitors; Immunotherapy; Immunotherapy Biomarkers; Kidney cancer; Ligands; Lung cancer; Lymphocytes, Tumor-Infiltrating - immunology; Male; Medical prognosis; Middle Aged; Prostate cancer; Prostatic Neoplasms - immunology; Retrospective Studies; Tumor Microenvironment; Tumors; United States > US; tumor microenvironment; tumor biomarkers; costimulatory and inhibitory T-cell receptors; prostatic neoplasms
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1136/jitc-2021-002455

BackgroundAlthough 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.MethodsImmunohistochemistry 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.ResultsHHLA2 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.ConclusionsBoth B7-H3 and HHLA2 have a critical impact on the immunosuppressive microenvironment, and the B7 score could be used as an independent prognostic factor for PCa. The B7 score combined with CD8+ TILs could be used as a new immune classification to stratify the risk of death, especially cancer-related death, for patients with PCa. These findings may provide insights that could improve response to immune-related comprehensive therapy for PCa in the future.