iProXProteomicsQiang ZuoMus <genus>http://www.iprox.org/page/project.html?id=IPX0014923000nfyyzq@126.comNanfang Hospital, Southern Medical UniversityiProXGastric cancer is one of the most prevalent cancers worldwide and is associated with a high mortality rate. Although immunotherapy has achieved some success for many tumor types, the limited response of gastric cancer to immunotherapy poses a challenge. Lactylation is a recently proposed post-translational modification derived from lactate that plays a key role in many physiological processes. In this study, we found that endoplasmic reticulum stress (ERS)-induced histone lactylation attenuated the immune response of dendritic cells (DC), decreased the ability of T cells to kill tumor cells, and enhanced tumor growth. Interestingly, ERS-induced H4K12 lactylation promoted the expression of PDIA6 in DC, leading to weakened immune activity of DC and decreased anti-tumor ability of T cells, thereby promoting gastric cancer immune evasion. Collectively, our work provides new insights into how ERS-induced lactylation modification attenuates the stability of DC to drive immune escape in gastric cancer and provides a promising biomarker for the efficacy of immunotherapy in gastric cancer.Endoplasmic reticulum stress-induced histone lactylation mediating immune escape of gastric cancer via PDIA6 overexpression in dendritic cells.Tu Chengshu C, Wu Ziqing Z, Zhong Xuxian X, Yang Shengnan S, Chen Xi X, Li Simin S, Xu Youqin Y, Zuo Qiang QfalseEndoplasmic Reticulum Stress-induced Histone Lactylation Mediating Immune Escape of Gastric Cancer via PDIA6 Overexpression in Dendritic CellsFirst, cell histones were extracted using a histone extraction kit (Solarbio, China), followed by the preparation of protein samples. Protein samples were then isolated by SDS-PAGE and stained with Richfast SDS-PAGE Staining Buffer (Prosperich, China). The colloids were cut for MS analysis to determine the location of the lactylation group.Tue Dec 30 00:00:00 GMT 2025PXD0725531008841896533