Transcription factor Zfx regulates tumor's evasion to T cell killing in immunotherapy.

ABSTRACT: Cancer immunotherapy aims to boost T cell responses against tumor cells. However, a large fraction of patients with cancer exhibit intrinsic or acquired resistance to immunotherapy. To better understand resistance mechanisms in tumor cells, we used CRISPR-Cas9 whole-genome screening to uncover tumor-specific genes that influence sensitivity to T cell killing. Among the top hits, we identified the transcription factor zinc-finger protein X-linked (Zfx). Zfx knockout tumor cells are resistant to T cell killing both in vitro and in vivo. We demonstrate that Zfx regulates expression of the apoptotic machinery, with Caspase-3 being a central element in mediating T cell killing. Mechanistically, our ChIP-Seq analyses in multiple human cancer cell lines show ZFX directly binds to th

SUBMITTER: Kaufmann U 

PROVIDER: S-EPMC12661158 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature