Abstract B83: A role of a transcription factor TOX in promoting CD8+ T-cell exhaustion in cancer via single-cell transcriptome analysis

Abstract

Abstract Recently to treat cancer, several cancer therapies have been developed such as chemotherapy, radiation therapy, immunotherapy, targeted therapy, and hormone therapy. Among several cancer therapies, immunotherapies have recently been developed and shown clinical impacts on a significant number of patients. However, even in the case of immunotherapy, every cancer therapy does not have a 100% response rate. Since the difference in the response rate is mainly due to tumor microenvironment, we need to understand the tumor microenvironment to overcome the low response rate of therapies. Previously, tumor microenvironment was analyzed using cell sorting techniques such as FACS, but it is hard to observe every cell subtype. However, recently, a new technique called single-cell RNA sequencing has been developed. Single-cell RNA sequencing sequences RNAs from every single cell from the sample. Using single-cell RNA sequencing, we can get transcriptome information from whole tumor sample. Therefore, we can observe interactions between the immune cells and the tumors cells using single-cell RNA sequencing. First of all, to focus on the microenvironment of tumor tissue, we analyzed public single-cell RNA sequencing data and unraveled the phenotype of exhausted T cells. By analyzing single-cell RNA sequencing data from the public, we found TOX, a T cell exhaustion-associated transcriptional regulator important for maintaining exhausted T cell. We confirmed that TOX is expressed in the context of exhausted T cell by FACS analysis. Also, using trajectory analysis, we observed expression pattern of TOX through T-cell exhaustion process. Additionally, we analyzed TCGA data to observe the effect of TOX on survival rate. Through analyzing several data such as expression data, binding assay, and open chromatin region of exhausted T cells, we found a potential role of the TOX gene. We also confirmed that the TOX gene can regulate the expression of other checkpoint molecules by knockdown experiment. Here, we found a novel regulator in the tumor microenvironment using single-cell transcriptomics. Citation Format: Kyungsoo Kim, Seyeon Park, Sang-Jun Ha, Insuk Lee. A role of a transcription factor TOX in promoting CD8+ T-cell exhaustion in cancer via single-cell transcriptome analysis [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr B83.