PD‐L1 and PD‐L2 expression in pancreatic ductal adenocarcinoma and their correlation with immune infiltrates and DNA damage response molecules

作者：Yue Zhang, Xianlong Chen, Shengwei Mo, Heng Ma, Zhaohui Lu, Shuangni Yu, Jie Chen · 发表于：The Journal of Pathology Clinical Research · 年份：2022 · DOI：10.1002/cjp2.259 · 被引用次数：40 · 研究领域：Cancer Immunotherapy and Biomarkers、Pancreatic and Hepatic Oncology Research、Glioma Diagnosis and Treatment

Abstract Immunotherapy targeting programmed cell death‐1 (PD‐1) has considerably improved the prognosis of patients with advanced cancers; however, its efficacy in the treatment of pancreatic ductal adenocarcinoma (PDAC) is unfavourable. To address the issue of PDAC immunotherapy, we investigated the expression of two PD‐1 ligands, PD‐L1 and PD‐L2, in PDAC, analysed their role in survival, and explored their correlation with clinicopathological features, immune infiltration, and DNA damage response molecules. Immunohistochemistry was performed on 291 surgically resected PDAC samples. In tumour cells (TCs) and immune cells (ICs), the positivity of PD‐L1 expression was 30 and 20% and that of PD‐L2 expression was 40 and 20%, respectively. Moreover, PD‐L1 expression on TCs correlated with its expression on ICs ( p < 0.0001); a similar result was observed for PD‐L2 ( p < 0.0001). Nonetheless, no correlation was observed between PD‐L1 and PD‐L2 expression. Positive PD‐L1 expression on TCs was related to N1 stage ( p = 0.011) and AJCC II stage ( p = 0.002), whereas positive PD‐L2 expression on TCs was associated with high FOXP3 + cell infiltration ( p = 0.001) and high BRCA2 expression ( p < 0.0001). Survival analysis revealed that positive PD‐L1 ( p = 0.046) and PD‐L2 ( p = 0.028) expression on TCs was an independent risk factor for unfavourable disease‐specific survival (DSS). Furthermore, positive PD‐L2 expression on TCs was an independent risk factor for lower DSS in th...