PD-L1 expression and tumor mutational burden status for prediction of response to chemotherapy and targeted therapy in non-small cell lung cancer

Journal of Experimental & Clinical Cancer Research

Ying Hu¹  Hui Zeng¹  Yanhui Chen¹  Henghui Zhang²  Zhiming Chen³  Jigang Dai⁴  Quanxing Liu⁴  Wenbo Han⁵  Yating Wang⁵  Wanning Yang⁵  Haitao Ma⁶ 

[1] 0000 0004 0369 153X, grid.24696.3f, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing Key Laboratory of Emerging Infectious Diseases, No.8 Jingshundongjie, 100015, Beijing, China;0000 0004 0369 153X, grid.24696.3f, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing Key Laboratory of Emerging Infectious Diseases, No.8 Jingshundongjie, 100015, Beijing, China;Genecast Precision Medicine Technology Institute, Huayuanbeilu 35, 100089, Beijing, China;0000 0004 1757 8861, grid.411405.5, Department of Thoracic Surgery, Huashan Hospital, 12 Wu Lu Mu Qi Road (M), 200040, Shanghai, China;Department of Thoracic Surgery, Xinqiao Hospital, Third Military Medical University (Army Medical University), 183 Xin Qiao Zheng jie, 400037, Chongqing, China;Genecast Precision Medicine Technology Institute, Huayuanbeilu 35, 100089, Beijing, China;grid.429222.d, Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, 215006, Suzhou, China;

关键词: PD-L1;    TMB;    Biomarker;    Targeted therapy;    Non-small cell lung cancer;    Prognosis;   

DOI  :  10.1186/s13046-019-1192-1

来源: publisher

【 摘 要 】

BackgroundSeveral targeted immunotherapies have recently showed significant advances in treatment of non-small cell lung cancer (NSCLC), including antibodies and inhibitors targeting programmed death-1 (PD-1) and its ligand (PD-L1).MethodsTumor tissue samples were prospectively collected from 183 patients with NSCLC including lung adenocarcinoma (ADC) and squamous cell carcinoma (SQCC). PD-L1 expression level was measured by immunohistochemistry assay and tumor mutational burden (TMB) status was assessed by next generation sequencing. Correlations between PD-L1 expressions, TMB status with clinicopathological characteristics were analyzed.ResultsPD-L1 expression was detected in 37% of ADC group and 55% in SQCC group while all clinicopathological characteristics were found comparable between these two groups. PD-L1 expression was negatively associated with overall survival in ADC group (P < 0.0001) but not in SQCC group (P = 0.418). In consistent with PD-L1 expression level, TMB status was significantly lower in ADC subjects as compared to SQCC subjects (P = 0.024) while PD-L1 positive subgroup and TMB high subgroup shared less subjects within ADC group than SQCC group. More importantly, the combination of TMB status and PD-L1 expression successfully identified responders, who showed significant longer median overall survival than non-responders (32 months vs. 8.5 months) in ADC subjects (P < 0.0001) but not in SQCC subjects.ConclusionsHere we tested the hypothesis that monitoring TMB, in addition to the existing PD-L1 expression level, could represent valuable non-invasive biomarkers for the chemotherapy and targeted therapy. Further analyses are in need to further assess the prognostic value of TMB for ADC and SQCC patients receiving immunotherapy.

【 授权许可】

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