ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2026
Histone H4K8 lactylation modulated immunosuppressive properties by promoting FAP transcription and ECM remodeling.
Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Lactylation in gastric cancer: From mechanisms to clinical applications (Review).Molecular medicine reports · 2026Review
- Lactylation Remodels Tumorigenesis, Immune Microenvironment, and Therapeutic Response.Current issues in molecular biology · 2026Review
- Lactate metabolism and protein lactylation in inflammatory and tumor microenvironments.Molecular biomedicine · 2026Review
- Unraveling the roles of fibroblast activation protein‑positive cancer‑associated fibroblasts in cancer: From mechanisms to therapy (Review).International journal of oncology · 2026Review
- Article
- Mechanical properties of the tumor microenvironment: drivers of immunotherapy resistance in solid tumors.Frontiers in immunology · 2026Review
- Identification of a lactylation-related gene signature in microsatellite stable gastric cancer based on bulk and single-cell RNA-seq.Frontiers in immunology · 2026Article
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Authors and funding
8 authors.
Funding
Abstract
BACKGROUND &
aimsThe role of histone lysine lactylation (Kla) in gastric cancer mesenchymal stromal cells (GCMSCs) remains elusive. This study aimed to investigate the potential lactyltransferase and the influence of histone Kla in GCMSCs.
methodsHistone Kla levels in GCMSCs were characterized by cell immunofluorescence and Western blotting. The transcriptional regulation was validated via CUT&Tag sequencing coupled with qPCR analysis. Immunosuppressive effectors through Western blotting and multiplex immunohistochemistry (mIHC). β-alanine and AZD3965 were applied to inhibit histone Kla in vitro. Ultimately, β-alanine was selected for its ability to enhance the efficacy of anti-PD-1 therapy in NCG
resultsThe primary GCMSCs exhibited higher histone Kla levels. Lactate treatment triggered the nuclear translocation of aminoacyl-tRNA synthetase 1 (AARS1), whose knockdown attenuated lactate-driven nuclear accumulation and suppressed histone Kla. CUT&Tag-qPCR analysis revealed lactate-induced Pan-Kla enrichment at the FAP promoter, driving extracellular matrix (ECM) receptor interaction pathways. Deeply, H4K8 lactylation (H4K8la) has been defined as the key regulatory role to promote FAP transcription, corroborated by mIHC mapping of their immune-excluded spatial organization. In NCG
conclusionsWe elucidate a Kla-dependent mechanism underlying GCMSCs-mediated ECM remodeling and immunosuppressive niche formation. The results provide novel insights into the epigenetic regulation of immunosuppressive TME.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.