Histone H3K18 Lactylation Drives Immunosuppression by Upregulating CD38 in Myeloid-Derived Suppressor Cells in Lung Cancer.

Authors

Yao Dai, Haiyan Dai, Yahui Wang, Wenxin Da, Yan Zhang, Wei Zhu, Deqiang Wang, Shengjun Wang, Jie Ma

Published in

Cancer immunology research. Sep 18, 2026. Epub Sep 18, 2026.

Abstract

Histone lactylation is an epigenetic modification that connects lactate metabolism with protein function. Our study identified lactate enhances the protein lactylation level not only in Myeloid-derived suppressor cells (MDSCs) of tumor-bearing mice, but also in the tumor tissues of lung cancer patients. This modification led to upregulation of CD38 expression and enhanced the immunosuppressive function of MDSCs. Mechanistically, CD38 promoted immunosuppression by depleting NAD⁺, and treatment with CD38 inhibitor or siRNA-mediated knockdown of CD38 in MDSCs delayed tumor progression. H3K18la is enriched at CD38 promoter region, with p300, HDAC1-3, and BRD4 identified as key epigenetic regulators in this process. Our findings reveal the critical role of the lactate-CD38-NAD⁺ axis in regulating MDSC immunosuppressive function and establish histone lactylation as an epigenetic mechanism controlling CD38 expression.

PMID:
42758124
Bibliographic data and abstract were imported from PubMed on 18 Sep 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.