Yanhui Chen1, Quanxing Liu2, Zhiming Chen3, Yating Wang4, Wanning Yang4, Ying Hu1, Wenbo Han4, Hui Zeng1, Haitao Ma5, Jigang Dai6, Henghui Zhang7,8. 1. Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing Key Laboratory of Emerging Infectious Diseases, No.8 Jingshundongjie, Beijing, 100015, China. 2. Department of Thoracic Surgery, Xinqiao Hospital, Third Military Medical University (Army Medical University), 183 Xin Qiao Zheng jie, Chongqing, 400037, China. 3. Department of Thoracic Surgery, Huashan Hospital, 12 Wu Lu Mu Qi Road (M), Shanghai, 200040, China. 4. Genecast Precision Medicine Technology Institute, Huayuanbeilu 35, Beijing, 100089, China. 5. Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, 215006, China. mht7403@163.com. 6. Department of Thoracic Surgery, Xinqiao Hospital, Third Military Medical University (Army Medical University), 183 Xin Qiao Zheng jie, Chongqing, 400037, China. 691057831@qq.com. 7. Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing Key Laboratory of Emerging Infectious Diseases, No.8 Jingshundongjie, Beijing, 100015, China. zhhbao@ccmu.edu.cn. 8. Genecast Precision Medicine Technology Institute, Huayuanbeilu 35, Beijing, 100089, China. zhhbao@ccmu.edu.cn.
Abstract
BACKGROUND: Several 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). METHODS: Tumor 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. RESULTS: PD-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. CONCLUSIONS: Here 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.
BACKGROUND: Several 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). METHODS:Tumor 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. RESULTS:PD-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. CONCLUSIONS: Here 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.
Authors: Vilde D Haakensen; Anand Khadse; Vandana Sandhu; Ann Rita Halvorsen; Steinar K Solberg; Lars H Jørgensen; Odd Terje Brustugun; Elin H Kure; Åslaug Helland Journal: Int J Cancer Date: 2020-06-17 Impact factor: 7.396