Author：Yanhui Chen, Yating Wang, Tao Zhou, Wanning Yang, Bohang Yang, Ying hu, Wenbo Han, Hui Zeng, Henghui Zhang
Background: Programmed cell death 1 ligand (PD-L1) expression and the tumour mutation burden (TMB) are distinct biomarkers of response to anti-PD-1/PD-L1 therapies. The proportion of PD-L1-positive, high-TMB patients and their overlap in newly diagnosed metastatic non-small cell lung cancer (NSCLC) and their effect on prognosis after receiving epidermal growth factor receptor (EGFR)-TKIs or platinum-based chemotherapy were evaluated.
Methods: One hundred eighty-seven NSCLC patients were included. Tumour tissue samples were collected to detect PD-L1 expression and TMB status by immunohistochemistry (using the SP142 antibody) and targeting next-generation sequencing of specific genes, respectively. Correlations between PD-L1 or TMB with clinicopathological characteristics were analysed.
Results: The PD-L1-positive rates of tumour cells were 37% (≥1%) and 20% (≥50%) in adenocarcinoma (ADC); 55% (≥1%) and 27% (≥50%) in squamous cell carcinoma (SQCC). PD-L1 in tumour cells was significantly associated with the SQCC subtype (P=0.030), male sex in ADC (P<0.001), wild-type ADC (P=0.049) and survival outcome of ADC (P<0.0001). The proportion of high TMB (≥13.7 mutations/Mb) in SQCC was higher than that of ADC (P=0.024). The TMB level did not correlate with survival. There were overlaps between high TMB and PD-L1 expression in patients of SQCC, wild-type ADC and EGFR-mutant ADC (22% vs. 10% vs. 3%, respectively), but the positive degree of PD-L1 did not correlate with TMB. The ADC PD-L1-negative plus low/moderate-TMB group had the longest survival time compared with those that were PD-L1 positive with low/moderate TMB or those that were PD-L1 positive with high TMB (41 mon vs. 8 mon vs. 7 mon, respectively; P<0.0001); this pattern was similar to that observed in wild-type ADC patients (32 mon vs. 6 mon vs. 8.5 mon, respectively; P=0.0005).
Conclusions: There were overlaps between the high-TMB and PD-L1-positive population, but the positive degree of PD-L1 did not correlate with the TMB value. PD-L1 expression was an independent predictor of poor prognosis in ADC patients, but the effect of TMB level on prognosis was small.