Data from H3K18 Lactylation Potentiates Immune Escape of Non–Small Cell Lung Cancer

• DOI: 10.1158/0008-5472.c.7523017
• Publication Date: 2024-11-04T08:41:32Z
• Authors: Cai Zhang; Lijie Zhou; Mingyuan Zhang; Yue Du; Cai Li; Huijun Ren; Lu Zheng
• Keywords: Immune escape

<div>Abstract<p>Recently discovered epigenetic modification lysine lactylation contributes to tumor development and progression in several types of cancer. In addition the tumor-intrinsic effects, histone may mediate microenvironment remodeling immune evasion. this study, we observed elevated pan–lysine H3 18 (H3K18la) levels non–small cell lung cancer (NSCLC) tissues, which was positively correlated with poor patient prognosis. Interruption glycolysis by 2-deoxy-D-glucose oxamate treatment silencing lactate dehydrogenase A B reduced H3K18la circumvented evasion NSCLC cells enhancing CD8<sup>+</sup> T-cell cytotoxicity. Mechanistically, directly activated transcription pore membrane protein 121 (POM121), enhanced MYC nuclear transport direct binding <i>CD274</i> promoter induce PD-L1 expression. a mouse xenograft model, combination therapy inhibitor an anti-PD-1 antibody induced intratumoral function exhibited strong antitumor efficacy. Overall, work revealed that potentiates escape activating POM121/MYC/PD-L1 pathway, offers insights into role posttranslational modifications carcinogenesis provides rationale for developing epigenetic-targeted strategy treating NSCLC.</p><p><b>Significance: </b>H3K18 supports immunosuppression non-small inducing POM121 increase activity expression, can be reversed metabolic reprogramming immunotherapy treatment.</p></div>