Please use this identifier to cite or link to this item: https://hdl.handle.net/11147/15413
Title: A MicroRNA-Regulated Transcriptional State Defines Intratumoral CD8+ Tcells That Respond To Immunotherapy
Authors: Tang, W.W.
Battistone, B.
Bauer, K.M.
Weis, A.M.
Barba, C.
Fadlullah, M.Z.H.
O'Connell, R.M.
Ekiz, Hüseyin Atakan
Keywords: Anti-Pd-1
Biomarker
Cd8<Sup>+</Sup> T Cell
Colorectal Cancer
Cp: Cancer
Cp: Immunology
Cxcr6
Immune Checkpoint Inhibition
Immunotherapy
Microrna-155
Ship-1
Tcf-1
Publisher: Elsevier B.V.
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 underlying miR-155-dependent CD8+ T cell transcriptional profile, we identify a gene signature that predicts ICI responses across 12 diverse cancers. Together, our findings support a model whereby miR-155 serves as a central regulator of CD8+ T cell-dependent cancer immunity and ICI responses that may be leveraged for future therapeutics. © 2025 The Author(s)
URI: https://doi.org/10.1016/j.celrep.2025.115301
https://hdl.handle.net/11147/15413
ISSN: 2639-1856
Appears in Collections:Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection

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