Yang Zhenlin, Peng Yue, Xu Jiachen, Chen Ping, Zhao Zhenshan, Cai Qingyuan, Li Lin, Tian He, Bai Guangyu, Liu Lei, Gao Shugeng, He Jie
Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 17 Panjiayuannanli, Beijing, China.
Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 17 Panjiayuannanli, Beijing, China; Department of Thoracic Surgery, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 Gongtinanlu, Beijing, China.
Transl Oncol. 2022 Oct;24:101501. doi: 10.1016/j.tranon.2022.101501. Epub 2022 Aug 1.
PVR/TIGIT and PD-L1/PD-1 axes play essential roles in tumor immune evasion and could be potential targets for combined immunotherapy. We aimed to evaluate the expression status of the above-mentioned immune markers in lung squamous cell carcinoma (LUSC), and investigate their survival impact and relevance with the immune microenvironment and clinicopathological features. We retrospectively collected specimens from 190 LUSC patients, who underwent pulmonary surgeries, and we performed immunohistochemistry assays of PVR, TIGIT, PD-L1, PD-1 and CD8. In our cohort, the positive rate of PVR was 85.8%, which was much higher than the positive rate of PD-L1 at 26.8%. A total of 32 (16.8%) patients demonstrated co-expression of PVR/PD-L1. High TIGIT density was correlated with positive PD-L1 expression, high PD-1 density, and high CD8 density (PD-L1, P=0.033; PD-1, P<0.001; CD8, P<0.001), and positive PVR expression was correlated with positive PD-L1 expression (P=0.046). High TIGIT density and high PVR/TIGIT expression were correlated with advanced TNM stage (TIGIT density, P=0.020; PVR/TIGIT expression, P=0.041). Patients with positive PVR expression, high TIGIT density, high PVR/TIGIT expression and PVR/PD-L1 co-expression exhibited a significantly worse prognosis (PVR, P=0.038; TIGIT, P=0.027; PVR/TIGIT, P=0.014; PVR/PD-L1, P=0.018). Multivariate analysis demonstrated that PVR/PD-L1 co-expression (Hazard ratio [HR], 1.756, 95% CI, 1.152-2.676, P=0.009) was an independent prognostic factor in LUSC patients. In conclusion, we demonstrated the expression status of PVR/TIGIT and PD-L1/PD-1 in LUSC. PVR/PD-L1 co-expression was an independent prognostic factor in LUSC patients and may serve as a potential predictive biomarker for dual-targeting immunotherapy.
PVR/TIGIT和PD-L1/PD-1轴在肿瘤免疫逃逸中起关键作用，可能是联合免疫治疗的潜在靶点。我们旨在评估上述免疫标志物在肺鳞状细胞癌（LUSC）中的表达状况，并研究它们对生存的影响以及与免疫微环境和临床病理特征的相关性。我们回顾性收集了190例行肺手术的LUSC患者的标本，并对PVR、TIGIT、PD-L1、PD-1和CD8进行了免疫组织化学检测。在我们的队列中，PVR的阳性率为85.8%，远高于PD-L1的阳性率26.8%。共有32例（16.8%）患者表现出PVR/PD-L1共表达。高TIGIT密度与PD-L1阳性表达、高PD-1密度和高CD8密度相关（PD-L1，P=0.033；PD-1，P<0.001；CD8，P<0.001），PVR阳性表达与PD-L1阳性表达相关（P=0.046）。高TIGIT密度和高PVR/TIGIT表达与晚期TNM分期相关（TIGIT密度，P=0.020；PVR/TIGIT表达，P=0.041）。PVR阳性表达、高TIGIT密度、高PVR/TIGIT表达和PVR/PD-L1共表达的患者预后明显较差（PVR，P=0.038；TIGIT，P=0.027；PVR/TIGIT，P=0.014；PVR/PD-L1，P=0.018）。多因素分析表明，PVR/PD-L1共表达（风险比[HR]，1.756，95%CI，1.152-2.676，P=0.009）是LUSC患者的独立预后因素。总之，我们展示了PVR/TIGIT和PD-L1/PD-1在LUSC中的表达状况。PVR/PD-L1共表达是LUSC患者的独立预后因素，可能作为双靶点免疫治疗的潜在预测生物标志物。
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