2024 World Conference on Lung Cancer (WCLC) - Posters-P3.03J.03 Genetic Signature Derived from Single-Cell Defined Microenvironment Remodeling Correlate with Efficacy of Neoadjuvant Immunotherapy in LUSC

P3.03J.03 Genetic Signature Derived from Single-Cell Defined Microenvironment Remodeling Correlate with Efficacy of Neoadjuvant Immunotherapy in LUSC

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This study investigates the role of neoadjuvant immunotherapy (NAI) combined with chemotherapy in improving prognosis for patients with lung squamous cell carcinoma (LUSC). It explores the dynamics of the tumor microenvironment (TME) remodeling that may contribute to treatment efficacy. By analyzing paired pre- and post-NAI samples from 40 LUSC patients, researchers extracted RNA and performed RNA sequencing to study immune cell infiltration.<br /><br />Key findings indicate that patients who achieved major pathological response (MPR) showed significant post-treatment increases in immune cells, such as NK cells, γδT cells, and activated B cells. Utilizing single-cell RNA sequencing data, 72 immune cell features helped categorize tumors into "hot" (immune-responsive) and "cold" (immune-suppressive) types. Patients with cold tumors were more likely to be non-MPR, implicating a less favorable therapeutic outcome.<br /><br />A genetic signature, comprising seven genes (ASS1, HOXC13, KLK1, NEFL, FOXL2, TNNT1, and LMX1B), was developed to predict transition to a cold tumor phenotype, which correlated with poorer treatment outcomes. High expression levels of these genes were associated with decreased immune cell infiltration post-NAI and a higher rate of non-MPR responses.<br /><br />Additionally, the predictive power of the seven-gene signature was validated externally using data from the OAK-LUSC cohort treated with atezolizumab, where lower expression corresponded with improved progression-free survival (PFS) and overall survival (OS).<br /><br />This study underscores the importance of TME remodeling in determining patient response to NAI and presents the seven-gene signature as a potential prognostic tool for guiding immunotherapy strategies in LUSC.

Asset Subtitle

Xing Li

Meta Tag

Speaker Xing Li

Topic Tumor Biology – Translational Biology

Keywords

neoadjuvant immunotherapy

lung squamous cell carcinoma

tumor microenvironment

RNA sequencing

immune cell infiltration

major pathological response

single-cell RNA sequencing

immune-responsive tumors

genetic signature

prognostic tool