Enhanced immunotherapy response in lung adenocarcinoma patients with COPD: insights into tumor cells and immune microenvironment characteristics.

Summary

Across a 248-patient immunotherapy cohort with single-cell and mfIHC validation, COPD-associated LUAD showed higher HLA-I on malignant cells and a more cytotoxic, immunoregulatory microenvironment. These features correlated with superior immunotherapy responses and were replicated in an independent 65-patient cohort.

Key Findings

• COPD-associated LUAD tumors showed elevated HLA-I expression on malignant cells.
• Tumor microenvironment was more active with increased NK cells and effector T-cell infiltration and immunoregulatory shifts.
• Improved immunotherapy responses in COPD patients were observed in a 248-patient cohort and replicated in an independent 65-patient cohort.
• Single-cell RNA-seq (187,123 cells) and mfIHC (34 patients) validated tumor and immune features.

Clinical Implications

COPD status and associated HLA-I/immune infiltration profiles could inform immunotherapy selection and monitoring in LUAD; prospective validation could refine patient stratification and combination strategies.

Limitations

• Observational design without randomization; potential residual confounding.
• Limited sample size for single-cell and mfIHC substudies; follow-up duration not detailed.

Future Directions

Prospective trials to validate COPD-informed biomarkers, mechanistic studies to modulate HLA-I and cytotoxic infiltration, and development of clinical tools for stratifying LUAD with COPD.