Objective:

To develop and validate an immune niche score based on immunohistochemistry (IHC) metrics that predicts major pathological response (MPR) to neoadjuvant chemoimmunotherapy in resectable non-small cell lung cancer (NSCLC).

Approach:

Key Findings:

• Overall, 146 patients (44.8%) achieved major pathological response (MPR) and 42 (12.9%) achieved pathological complete response.
• MPR was associated with higher TLS maturity, CD8+ cells within 50 μm of TLS, higher CD8/FOXP3 ratio, and lower CD163/CD68 ratio.
• In external validation, the immune niche score achieved an AUC of 0.732 (95% CI, 0.648–0.816), outperforming the clinical model (AUC 0.564), PD-L1 alone (AUC 0.635), clinical + PD-L1 (AUC 0.613), and XGBoost (AUC 0.692).

Interpretation:

The IHC-derived immune niche score shows moderate performance in predicting MPR after neoadjuvant chemoimmunotherapy in resectable NSCLC.

Limitations:

• The study is retrospective and conducted at two centers, which may limit generalizability.
• Further multicenter and prospective validation is needed to confirm findings.

Conclusion:

The immune niche score may provide a more comprehensive assessment of tumor immune context than PD-L1 TPS alone.

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