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

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 marg...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381330/
https://www.ncbi.nlm.nih.gov/pubmed/34417325
http://dx.doi.org/10.1136/jitc-2021-002455
Descripción
Sumario: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 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.