Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Xin Zhang , Jiayu Liu , Xin Zhao , Li Sun , Chuang Liu , Yaxuan Zhang , Pengyao Du , Fanfan Meng , Ling Li
Background: Immune checkpoint blockade are recommended in more and more solid tumors for first-line or posterior treatment, and PD-L1 expression is a crucial predictive biomarker for immunotherapy. However, the expression can be influenced by many factors. Methods: A total of 1743 Chinese patients with solid tumor was retrospectively identified. The Dako PD-L1 IHC 22C3 pharmDx assay was used to detect PD-L1 protein expression. And Tumor Proportion Score (TPS) ≥ 1% was defined as positive expression, TPS ≥ 50% was defined as high expression. Genomic profiling was performed on tumor tissue and matched peripheral blood samples. Only the tumor subtypes with sufficient sample size were used for correlation analysis. Results: PD-L1 positive expression occurred in 45.6% patients and high expression occurred in 8.1% patients. The highest expression incidences occurred in cervical cancer as of 78.8%, followed by lung cancer (53.8%), esophageal cancer (53.7%) and gastric cancer (42.7%). The PD-L1 expression assessed by TPS was consistent with that assessed by Combined Positive Score (CPS) in multiple tumors. However, it was significantly different in gastrointestinal tumors, especially in colorectal cancer (TPS>1%: 30.4% vs. CPS>1: 80.6%). In addition, gene alternations including TP53, CDKN2A, LRP1B, KRAS and PIK3CA apparently occurred in patients with high PD-L1 expression. Moreover, high tumor mutation burden (TMB-H) was associated with PD-L1 positive expression in these Chinese patients. Besides, no correlation was found between microsatellite instability (MSI) and PD-L1 expression. Conclusions: Our results illustrated genomic correlates of PD-L1 expression in Chinese solid tumor patients. These findings may broaden the application of immune checkpoint blockade to patients harboring specific molecular characteristics.
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