ArticlebioRxiv : the preprint server for biology2026
Tumor-infiltrating natural killer cell profiling for therapeutic stratification in patients with resectable non-small cell lung cancer.
Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Objective: Neoadjuvant chemoimmunotherapy has improved outcomes in resectable non-small cell lung cancer (NSCLC), yet its real-world implementation is often challenged by surgical delays, immune-mediated fibrosis, and postoperative complications. Smokers with NSCLC, despite a high risk for surgical morbidity, show enhanced responses to neoadjuvant chemoimmunotherapy. This study aimed to identify smoking-associated immune cell determinants that could guide treatment strategies. Methods: Single-cell RNA sequencing (scRNAseq) was performed on 61 lung tissues from non-smokers and smokers to identify smoking-related immune compositions. The scRNAseq data from 19 invasive lung adenocarcinomas were used to validate their presence in the tumor-immune microenvironment. Bulk RNA sequencing data from 102 resected NSCLC and 24 NSCLC patients treated with neoadjuvant chemoimmunotherapy followed by surgery were used for Results: Among 135 lung cellular phenotypes, two natural killer (NK) cell subsets were strongly associated with smoking and chronic obstructive pulmonary disease (COPD) severity. "Stress-responsive" NK (NK Conclusions: Intratumoral NK cell phenotyping may aid in therapeutic stratification in patients with NSCLC. NK
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