Genomic discordances and heterogeneous mutational burden, PD-L1 expression and immune infiltrates of non-small cell lung cancer metastasis

Abstract

AimsTo investigate the genomic discordances and heterogeneous mutational burden, PD-L1 expression and immune cell (IC) infiltrates of non-small cell lung cancer (NSCLC) metastasis.MethodsSurgical samples from 41 cases of NSCLC with metastatic tumours (MTs) and paired primary tumours (PTs) were collected. PD-L1 expression and ICs were quantified using image-based immunohistochemistry profiling. Whole exome sequencing was employed to explore discrepancies in genomic characteristics, tumour mutational burden (TMB) and tumour neoantigen burden (TNB) in 28 cases.ResultsNon-synonymous mutations in MTs were slightly more than in PTs, with only 42.34% of mutations shared between paired PTs and MTs. The heterogeneity of TMB showed no significant difference (p=0.785) between MTs and PTs, while TNB significantly increased in MTs (p=0.013). MTs generally exhibited a higher density of PD-L1+ cells and a higher tumour proportion score with a lower density of IC infiltrates. Subgroup analysis considering clinicopathological factors revealed that the heterogeneity of immune biomarkers was closely associated with the histology of lung adenocarcinoma, metastatic sites of extrapulmonary, time intervals and treatment history. Prognosis analysis indicated that a high density of CD8+ T cells was a low-risk factor, whereas a high density of PD-L1+ cells in MTs was a high-risk factor for cancer-related death in metastatic NSCLC.ConclusionsThe mutational burden, PD-L1 expression and IC infiltrates undergo changes during NSCLC metastasis, which may impact the immunotherapeutic benefits in patients with NSCLC with metastatic progression and should be monitored according to clinical scenarios.