A microRNA-regulated transcriptional state defines intratumoral CD8⁺ T cells that respond to immunotherapy.

ABSTRACT: The rising incidence of advanced-stage colorectal cancer (CRC) and poor survival outcomes necessitate new and effective therapies. Immune checkpoint inhibitors (ICIs), specifically anti-PD-1 therapy, show promise, yet clinical determinants of a positive response are suboptimal. Here, we identify microRNA-155 (miR-155) as necessary for CD8⁺ T cell-infiltrated tumors through an unbiased in vivo CRISPR-Cas9 screen identifying functional tumor antigen-specific CD8⁺ T cell-expressed microRNAs. T cell miR-155 is required for anti-PD-1 responses and for a vital intratumor CD8⁺ T cell differentiation cascade by repressing Ship-1, inhibiting Tcf-1 and stemness, and subsequently enhancing Cxcr6 expression, anti-tumor immunity, and effector functions. Based on an unde

SUBMITTER: Tang WW 

PROVIDER: S-EPMC11924119 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature