LIM-domain-only 4 (LMO4) enhances CD8⁺ T-cell stemness and tumor rejection by boosting IL-21-STAT3 signaling.

ABSTRACT: High frequencies of stem-like memory T cells in infusion products correlate with superior patient outcomes across multiple T cell therapy trials. Herein, we analyzed a published CRISPR activation screening to identify transcriptional regulators that could be harnessed to augment stem-like behavior in CD8⁺ T cells. Using IFN-γ production as a proxy for CD8⁺ T cell terminal differentiation, LMO4 emerged among the top hits inhibiting the development of effectors cells. Consistently, we found that Lmo4 was downregulated upon CD8⁺ T cell activation but maintained under culture conditions facilitating the formation of stem-like T cells. By employing a synthetic biology approach to ectopically express LMO4 in antitumor CD8⁺ T cells, we enabled selective

SUBMITTER: Schelker RC 

PROVIDER: S-EPMC11310520 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature