556 Transcription factor Zfx regulates tumor’s evasion to T cell killing in immunotherapy

• DOI: 10.1136/jitc-2024-sitc2024.0556
• Publication Date: 2024-11-05T14:58:58Z
• Authors: Ulrike Kaufmann; Joy Wang; Marinella G Callow; Jean-Philippe Fortin; Szymon Myrta; Dorothee Nickles; Eric Cheng; Yuxin Liang; Scott Martin; Mike Costa; Haochu Huang
• Keywords: Evasion (ethics)

<h3>Background</h3> A large fraction of patients with cancer exhibit an intrinsic or acquired resistance to immunotherapies that aim at boosting T cell responses against tumor cells. <h3>Methods</h3> To better understand mechanisms in cells, we used CRISPR-Cas9 whole-genome editing identify modified cells are resistant killing. <h3>Results</h3> Among the top hits, identified transcription factor zinc-finger protein X-linked (Zfx). Zfx knockout killing both <i>in vitro</i> and vivo</i>. Mechanistically showed regulates expression genes involved apoptosis pathways Caspase-3 is one central components regulated by Zfx. In addition, ZFX decreased several human tissues compared healthy tissues. Female kidney renal clear carcinoma (KIRC) high longer survival low expression. <h3>Conclusions</h3> Our results demonstrate a novel mechanism suggest targeting combination immune therapies could benefit patients.