WCLC 2025 - Posters & ePosters-EP.07.45 Single-Cell Analysis Revealed the Characteristics of Tumors With Different Responses to Neoadjuvant Chemo Immunotherapy in Stage II-IIIB NSCLC

EP.07.45 Single-Cell Analysis Revealed the Characteristics of Tumors With Different Responses to Neoadjuvant Chemo Immunotherapy in Stage II-IIIB NSCLC

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This study investigated the tumor and immune microenvironment characteristics associated with different responses to neoadjuvant chemo-immunotherapy (NCIT) in stage II-IIIB non-small cell lung cancer (NSCLC) patients without EGFR/ALK/ROS1 mutations. Thirty patients received up to four cycles of tislelizumab combined with platinum-based chemotherapy before surgery. Single-cell RNA sequencing was performed on over 473,000 cells from pre- and post-treatment tumor and adjacent tissues, and patients were classified by pathological complete remission (pCR) status.<br /><br />The overall response rate was 83.3%, with a 100% disease control rate. Among 20 surgically treated patients, major pathological remission (MPR) occurred in 80% and pCR in 50%. The single-cell analysis revealed that tumors from the pCR group had significantly higher proportions of cytotoxic T cells, TH17 cells, and type II alveolar cells, while the non-pCR group showed increased regulatory and exhausted T cells. Notably, after NCIT, cytotoxic T cell proportions decreased in pCR patients, but natural killer T (NKT) cells increased, implicating NKT cells in treatment efficacy. In contrast, tumor-associated fibroblasts expanded markedly in non-pCR tumors after therapy, potentially contributing to resistance.<br /><br />Trajectory analysis of tumor cells demonstrated distinct evolutionary paths in responders versus non-responders. These findings highlight distinct immune landscapes and tumor cell dynamics associated with therapeutic outcomes. The study provides novel insights into cellular and molecular determinants of NSCLC responsiveness to neoadjuvant chemo-immunotherapy, offering a framework for future personalized treatment strategies to improve efficacy and overcome resistance.

Asset Subtitle

Minglei Zhuo

Meta Tag

Speaker Minglei Zhuo

Topic Early-Stage Non-small Cell Lung Cancer

Keywords

non-small cell lung cancer

neoadjuvant chemo-immunotherapy

tislelizumab

single-cell RNA sequencing

pathological complete remission

cytotoxic T cells

natural killer T cells

tumor-associated fibroblasts

tumor microenvironment

immune cell dynamics