BackgroundNeoadjuvant chemoimmunotherapy improves pathological response in resectable non-small cell lung cancer (NSCLC), but response remains heterogeneous. PD-L1 tumor proportion score (TPS) incompletely captures spatial immune contexture.
We developed and cross-center validated an immunohistochemistry (IHC)-derived equal-weight immune niche score integrating tertiary lymphoid structure (TLS) maturity, CD8–TLS proximity, CD8/FOXP3 balance, CD163/CD68 ratio, and PD-L1 TPS.MethodsThis two-center retrospective cohort included 326 patients with resectable NSCLC treated with neoadjuvant chemoimmunotherapy. The model-development cohort included 188 patients, and an institution-level external-validation cohort within the same regional medical system included 138 patients.
The primary endpoint was major pathological response (MPR). Model performance was evaluated using discrimination, calibration, decision curve analysis, and ablation analysis.
Sensitivity analyses tested alternative CD8–TLS thresholds, ICI-agent subgroups, missing-data approaches, Granzyme B incorporation, and alternative weighting. Exploratory analyses assessed event-free survival (EFS), overall survival (OS), interobserver reproducibility, and asthma-related pulmonary safety.ResultsOverall, 146 patients (44.8%) achieved MPR and 42 (12.9%) achieved pathological complete response.
MPR tumors had higher TLS maturity, CD8+ cells within 50 μm of TLS, CD8/FOXP3 ratio, PD-L1 TPS, lower CD163/CD68 ratio, and higher immune niche score.
Frontiers in Immunology published a clinical update in Infectious Disease on 19 Jun 2026.
The item focuses on An IHC-derived TLS–CD8–macrophage immune niche score predicts major pathological response to neoadjuvant chemoimmunotherapy in resectable NSCLC.
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