Background
Immune checkpoint inhibitors (ICIs) are standard therapies for patients with advanced lung adenocarcinoma and significantly improve treatment outcomes. The effect of tobacco smoking on the response of immune checkpoint inhibitors is somewhat diverging. Here, we assessed the impact of tobacco exposure on the tumor microenvironment and developed a feasible tool for predicting prognosis.
Conclusion
Our analysis provides further insight into the profound impacts of tobacco exposure on tumor immune microenvironment and envisions integrative predictive models of RFscore, predicting the prognosis of smoking lung adenocarcinoma, which might help to understand the potential mechanism of smoking exposure on tumor immune microenvironment.
Methods
Whole exon sequence data and the corresponding clinical information were downloaded from the Cancer Genome Atlas. The signature was developed by the Random Forest algorithm. CIBERSORTx online tool was used to estimate immune infiltration. Functional assays were performed to assess the roles of tobacco exposure in cancer cells. Immunohistochemistry (IHC) was performed to identify and validate the immune activation status.
Results
The TMB of lifelong non-smoker, current reformed smoker for over 15 years, current reformed smoker<15 years and current smoker had a significantly increasing trend in LUAD patients. In vitro tobacco exposure promoted the expression of PD-L1 and malignant phenotype of LUAD cells. In addition, patients with high Random Forest score (RFscore) had a poorer prognosis than those with low RFscore. The ROC curve analysis of RFscore revealed a promising prognostic capability. Memory activated CD4 + T cells, CD8 + t cells and memory B cells were noticeably enriched in the high RFscore group and PDCD1 appreciably upregulated in the high RFscore group as well. Furthermore, IHC results suggested that patients with high RFscore remained an immune activation status, indicating a positive correlation between RFscore and patient's immune status.