Abstract 5223: Deciphering cellular heterogeneity and therapeutic responses in NSCLC through scRNA-seq analysis

Abstract Programmed cell death protein and its ligand (PD-1 / PD-L1) blockades have been approved for the treatment of metastatic non-small cell lung cancer (NSCLC). PD-L1 binds to PD-1 and functions as a co-inhibitory factor. It is well known that in cancer, PD-L1 is highly expressed hence cancer cells can evade the host immunity in the tumor microenvironment (TME). Although PD-1 / PD-L1 blockades have been clinically utilized, the biological factors determining treatment outcome remain convoluted. An in-depth investigation of cellular heterogeneity including both cell subtypes and states (defined by cellular biomolecular programming) will provide foundational evidence for clinicians and researchers to improve PD-1 / PD-L1 immunotherapeutic practice. The recent decade has shown an explosive growth of single-cell RNA sequencing (scRNA-seq) to study biomedical phenomena. In contrast to bulk RNA-seq, scRNA-seq enables researchers to properly decipher and analyze the complex cellular heterogeneity. Our scRNA-seq data spans 674, 609 cells populating early, late, metastatic stage lung cancer and the normal lung tissues from 100 subjects. Especially, part of our metastatic samples harbor classification based on the existence of immune checkpoint blockade (ICB) treatment and therapeutic efficacy of the treatment. Our scRNA-seq analysis results thoroughly provide an intensive comprehension of dysregulation in T cells. This single-cell analysis potentially reveals pathways targeted by immunotherapy and discovers possible therapeutic targets which could be combined with the current immunotherapy for the synergistic effects. Citation Format: Hwajin Choi, Kyoung-Ho Pyo, Sun Min Lim, Byoung Chul Cho, Seunghee Hong. Deciphering cellular heterogeneity and therapeutic responses in NSCLC through scRNA-seq analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5223.