Tumor immune microenvironment analysis in different pathologic responses to neoadjuvant immunotherapy combined with chemotherapy in non-small cell lung cancer.

BACKGROUND: Lung cancer, particularly non-small cell lung cancer (NSCLC), remains a major global challenge. Neoadjuvant immunotherapy combined with chemotherapy (IO-CT) has shown potential in improving survival outcomes for resectable NSCLC. This study aimed to investigate changes in the tumor immune microenvironment (TIME) following IO-CT or chemotherapy alone and identify immune biomarkers predictive of treatment response. METHODS: Pre- and post-treatment tumor samples from NSCLC patients receiving either IO-CT or chemotherapy alone were analyzed. Multiplex immunofluorescence was performed to assess immune cell populations, including CD3(+) T cells, CD8(+) T cells, CD8(+) programmed death 1 (PD-1)(+) T cells, and CD20(+) B cells. The presence of tertiary lymphoid structures (TLS) and immune cell infiltration patterns was correlated with treatment responses, including major pathologic response (MPR) and pathologic complete response (pCR). RESULTS: IO-CT preserved and enhanced immune cell populations, particularly CD3(+) T cells, CD8(+) T cells, and CD8(+) PD-1(+) T cells, while promoting TLS formation, which was associated with improved survival outcomes. Patients achieving MPR/pCR displayed higher baseline infiltration of CD20(+) B cells and cytotoxic T lymphocytes (CTLs), suggesting a pre-existing "immune activation" state predictive of treatment response. CONCLUSIONS: This study highlights the role of TIME reprogramming and TLS formation in the efficacy of neoadjuvant IO-CT for NSCLC. Baseline immune activation, marked by CD20(+) B cells and CTLs, may serve as predictive biomarkers for treatment response, paving the way for personalized treatment strategies and improved prognostication.