According to genetic and genomic analysis as well as previous clinical research, lung cancer in never-smokers might have pathogenesis and progression different from that of lung cancer among smokers. There has been indirect evidence that different types of mutations in tumors might be related to the altered immune functions.
Tissues from 110 female patients with lung adenocarcinoma (never-smokers: 102 & smokers: 8) at the Samsung Medical Center, were analyzed by next-generation genomic sequencing including whole-exome seq and RNA-seq. Somatic mutations and gene expression levels of immune signature genes were profiled. The significance for clinical outcome of the selected genes was plotted using Kaplan-Meier method and log-rank test.
Expression biomarkers of immune suppressive cells such as mast cells, macrophage and Treg were prominent in female never-smokers compared to female smokers of lung adenocarcinoma. The data suggest that cells of cytotoxic functions are deactivated in smokers, whereas cells of immune suppressive functions are activated in never-smokers. Specifically as expression of immune markers specific for B-cells, dendritic cells, mast cells and Treg was especially up-regulated (p
This overall immune suppression in lung adenocarcinoma patients with EGFR mutation might explain the lower response rate of anti-PD-1/PD-L1 blockade to the female never smokers, which suggests that other approaches to block the immune suppressive microenvironment would be necessary.
Clinical trial identification
Legal entity responsible for the study
The Institutional Review Board of Samsung Medical Center
Samsung Cancer Research Institute
All authors have declared no conflicts of interest.