Abstract 35P
Background
The emergence of immune checkpoint inhibitors (ICIs) has opened a new chapter for the treatment of non-small cell lung cancer (NSCLC). Smoking status has been repeatedly confirmed to affect the efficacy of ICIs in NSCLC patients, but the specific mechanism is still unclear.
Methods
We performed bioinformatics analysis on the Memorial Sloan Kettering Cancer Center (MSKCC) clinical NSCLC cohort receiving ICIs treatment, the Cancer Genome Atlas (TCGA)-Pang lung cancer cohort and Gene Expression Omnibus (GEO) database cohort that did not receive ICIs treatment, including: survival prognosis, gene mutation, copy number variation(CNV), immunogenicity, immune microenvironment, etc., explored the impact of smoking status on the prognosis of NSCLC patients treated with ICIs and possible mechanism. In addition, NSCLC surgical samples were also collected for Mass Cytometry (cyTOF) experiment to verify the mechanism. Finally, three drug sensitivity databases are predicted to further explore the best possible combination of therapeutic effects under different smoking conditions.
Results
Through the analysis of the NSCLC cohort treated with ICIs in MSKCC, it was found that the previous or current smokers in NSCLC receiving ICIs treatment had a longer Progression-Free Survival (PFS, HR: 0.69, 95% CI: 0.49-0.97, P=0.031) than those who never smoked. Further analysis of the validation cohorts found that the differences in prognosis between different groups may be related to the smoking group's higher immunogenicity, higher gene mutations, and stronger immune microenvironment. The results of the cyTOF experiment also further prove the immune microenvironment of smoking NSCLC patients is activated.The prediction of common chemotherapy drugs suggests that non-smokers with poor efficacy of ICIs are more suitable for chemotherapy or targeted drug therapy.
Conclusions
Our research results suggest that among NSCLC patients receiving ICIs treatment, the stronger immunogenicity and activated immune microenvironment of the smoking group make their prognosis better.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Jian Zhang.
Funding
Zhujiang Hospital.
Disclosure
All authors have declared no conflicts of interest.