Abstract 2278: Unraveling immune dynamics of CD4+ in non-small cell lung cancer through single-cell analysis and gene expression profiling

Abstract

Abstract Non-small cell lung cancer (NSCLC) is a type of epithelial lung cancer other than small cell lung cancer and represents the majority of cases in lung cancer. The immune response against NSCLC relies significantly on the vital role by CD4+ T cells, contributing to the regulation of immune system and the suppression of tumor growth. Various CD4+ T cell subtypes, such as T conventional cells (Tconv cells) and T regulatory cells (Treg cells), perform distinct functions within the immune system. Tconv cells boost immune responses against specific pathogens, while Treg cells play a role in suppressing immune reactions. Investigating the correlation between Tconv cells and Treg cells in NSCLC could serve a valuable biomarker for evaluating the immune status of lung cancer patients. We examine the connection between particular CD4+ T cells in the lung and specific gene expressions associated with NSCLC. Through single-cell analysis, we classified the proportions of Treg cells and Tconv cells within CD4+ T cells in both the lungs and spleen of mice. Our discovery revealed that the proportion of Tconv cells in the lungs exceeded that in the spleen. From the differential gene expression (DEG) analysis using RNA-Seq data for Treg cells and Tconv cells in NSCLC, compared to the control group of Peripheral Blood Mononuclear Cells (PMBC), we identified 1823 genes uniquely expressed in NSCLC Treg cells and 711 genes in Tconv cells. Within these genes, we verified the expression of IL2RA and CTLA4, known to be expressed in NSCLC. Additionally, we identified high expression of genes TM4SF1 and KRT6A. By comparing the genes specific to Tconv and Treg cells in the lungs with those significantly expressed in NSCLC, we were able to identify 114 co-expressed genes in Treg cells and 71 in Tconv cells. We conducted GO and KEGG pathway analyses on these genes and examined the interaction networks among the associated genes. Furthermore, we found receptor interactions between Tconv cell subtypes (Th1, Th2, Th17, and Tfh) and Treg cells through cell-cell interaction analysis. We explored the mouse phenotypes associated with these genes. These discoveries unveiled connections within lung-specific gene networks of Treg and Tconv cells associated with NSCLC, highlighting candidate genes for targeted therapy in cancer. Citation Format: Hyunmin Woo, JiHye Yang, Siyoung Yang, Seong-il Eyun. Unraveling immune dynamics of CD4+ in non-small cell lung cancer through single-cell analysis and gene expression profiling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2278.