p53 和 LKB1 的免疫组化分析作为非小细胞肺癌免疫检查点抑制剂反应的预测生物标志物

Immune checkpoint inhibitors (ICIs) are a mainstay in the treatment of non-small cell lung cancer (NSCLC). Although accurate predictive biomarkers are required for treatment selection-considering the risk of serious immune-related adverse events-such predictors remain limited. In this study, we aimed to evaluate the association between the expression of p53, LKB1, and NRF2 proteins and ICI efficacy.

This retrospective analysis included patients with NSCLC who received first-line ICI-based therapy or epidermal growth factor receptor-tyrosine kinase inhibitors between 2017 and 2025 at our institute. Immunohistochemistry was performed on diagnostic samples to assess p53, LKB1, and NRF2 expression and tumor-infiltrating lymphocytes (TILs). Additionally, the associations between biomarker expression and clinical outcomes were examined.

Among the 43 evaluable cases in the ICI group, aberrant p53 expression was observed in 46.5%, LKB1 loss in 13.9%, and nuclear-dominant NRF2 expression in 34.9% of cases. Aberrant p53 expression was associated with increased TILs and improved progression-free survival (PFS), while the loss of LKB1 was correlated with an immunosuppressive microenvironment and shorter PFS. Nuclear-dominant NRF2 expression was associated with poorer overall survival.

The immunohistochemical profiles of p53 and LKB1 are associated with distinct immune microenvironment features. These markers may serve as surrogate predictors of ICI efficacy in patients with NSCLC.