Joint single-cell transcriptomic and epigenomic analysis reveals key regulators of CAR T cell stemness and antitumor immunity
Year: 2024
Type: conference-abstract
Abstract: The differentiation of antitumor T cells is tightly controlled by transcriptional and epigenetic pathways. Understanding the programs governing the differentiation of therapeutic T cells such as chimeric antigen receptor (CAR) T cells is crucial for improving their efficacy. Using a single-cell multi-omics approach, we simultaneously profiled chromatin accessibility and transcription within the same single CAR T cell in mice with B-cell leukemia or melanoma. One of the CAR T-cell subsets displayed stem cell-like properties and greater proliferative potential upon tumor challenge. In addition, we uncovered primed chromatin states foreshadowing transcriptional changes and lineage-defining genes heavily regulated at the epigenetic level. By constructing gene regulatory networks in CAR T cells based on the single-cell multi-omics data, we identified hub transcription factors of stem-like CAR T cells including BACH2. By knocking out BACH2 in CAR T cells, we demonstrated an essential role of BACH2 in the development of the stem-like subset and antitumor immunity of CAR T cells. Thus, our study elucidated the transcriptional and epigenetic mechanisms underlying CAR T-cell differentiation and revealed key transcriptional regulators controlling the differentiation and antitumor immunity of CAR T cells.
Source: The Journal of Immunology
Authors: Tuoqi Wu, Ziang Zhu, Safuwra Wizzard, Chen Yao
Institution: The University of Texas Southwestern Medical Center
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4404174046