CRISPR screens define unified hallmarks of cancer cell-autonomous immune evasion

Huber, A; Djajawi, TM; Rivera, IS; Vervoort, SJ; Kearney, CJ

Author(s): Huber, A; Djajawi, TM; Rivera, IS; Vervoort, SJ; Kearney, CJ;
Details: Publication Year 2026-01-27,Volume 45,Issue #1,Page 116738
Journal Title: Cell Reports
Abstract: Cancer immunotherapy has transformed cancer treatment, yet only a minority of patients achieve durable benefit. Although early efforts to enhance immunotherapy focused on boosting immune effector function, reversing T cell exhaustion, or altering the tumor microenvironment, it is now clear that cancer cell-autonomous mechanisms play a major role in immune escape. Such programs, driven by the cancer cell genome, transcriptome, and epigenome, include desensitization to cytokine signaling, such as interferon (IFN)gamma and tumor necrosis factor (TNF); impaired antigen presentation; upregulation of suppressive ligands such as programmed cell death ligand 1 (PD-L1); and epigenetic silencing of immunogenic pathways. The rise of high-throughput functional genomics, especially in vitro and in vivo CRISPR-based screening, has greatly expanded our ability to map these pathways and define how tumors evade CD8(+) T cell-mediated pressure. A deeper understanding of these cancer cell-autonomous immune-evasion mechanisms will be essential for developing new therapeutic strategies that broaden the impact of immunotherapy across diverse cancers.
Publisher: Cell Press
Keywords: Humans; *Neoplasms/immunology/genetics/pathology; *Tumor Escape/genetics; *CRISPR-Cas Systems/genetics; Tumor Microenvironment/immunology; Immunotherapy; Animals; *Immune Evasion; *Clustered Regularly Interspaced Short Palindromic Repeats/genetics; CD8-Positive T-Lymphocytes/immunology; CP: Cancer; CP: Immunology
Research Division(s): Genetics and Gene Regulation
PubMed ID: 41417728
Publisher's Version: https://doi.org/10.1016/j.celrep.2025.116738
Open Access at Publisher's Site: https://doi.org/10.1016/j.celrep.2025.116738
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-01-22 09:58:55

Last Modified: 2026-02-09 09:24:34