期刊
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
卷 38, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s13046-019-1192-1
关键词
PD-L1; TMB; Biomarker; Targeted therapy; Non-small cell lung cancer; Prognosis
类别
资金
- National Key Sci-Tech Special Project of China [2018ZX10302207]
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 (32months vs. 8.5months) 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.
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