WCLC 2025 - Posters & ePosters-P3.01.37 Time-Dependent Analysis Reveals the Dual Role of Smoking in Non-Small Cell Lung Cancer Immunotherapy

Pdf Summary

This study investigates the complex role of smoking history in non-small cell lung cancer (NSCLC) patients undergoing immunotherapy. While smoking is a recognized risk factor for lung cancer, its impact on the effectiveness of immunotherapy remains unclear. The researchers analyzed patient data from Guangdong Provincial People’s Hospital, dividing cases into small cell lung cancer (SCLC) and NSCLC groups. They employed Kaplan-Meier survival analysis and time-dependent Cox regression (due to non-proportional hazards evidenced by Schoenfeld residuals) to assess how smoking history influenced progression-free survival (PFS) during immunotherapy.<br /><br />Results revealed a dual, time-dependent effect of smoking in NSCLC patients: smoking provided short-term protective effects during early disease progression, but a beneficial impact on long-term progression was also observed. In contrast, smoking history had no notable effect on SCLC outcomes. Further investigation using Mendelian Randomization (MR) and single-cell immune profiling showed that smoking increased the presence of both activated immune cells and exhausted/tolerant immune cells in NSCLC, potentially explaining the observed dual effects. These immune changes suggest that smoking modulates the tumor immune microenvironment dynamically, influencing immunotherapy responses variably over time.<br /><br />Quantitative data indicated that never smokers had a higher hazard ratio for early progression compared to current smokers, but this reversed over longer follow-up periods, highlighting the complex prognostic nature of smoking status. The study provides novel insights into the intricate interplay between smoking-related immune modulation and immunotherapy efficacy in NSCLC, emphasizing the need to consider smoking history as a factor with both protective and adverse temporal components. The findings underscore the importance of timing and immune context in tailoring immunotherapeutic strategies for lung cancer patients with differing smoking backgrounds.

Asset Subtitle

Ying-Long Peng

Meta Tag

Speaker Ying-Long Peng

Topic Risk Factors, Risk Reduction & Tobacco Control

Keywords

non-small cell lung cancer

NSCLC

smoking history

immunotherapy

progression-free survival

Kaplan-Meier analysis

Cox regression

Mendelian Randomization

tumor immune microenvironment

immune cell profiling