GFPT1 facilitates immune escape in lung adenocarcinoma by promoting the O-GlcNAcylation of MYC and regulating PD-L1
- Exp Cell Res. 2026 Jun 15;459(2):115024. doi: 10.1016/j.yexcr.2026.115024.
- 1. Department of Oncology, Graduate School, Hebei Medical University, Shijiazhuang, Hebei, 050011, China; Oncology Department II, Cangzhou People's Hospital, Cangzhou, Hebei, 061000, China.
- 2. Oncology Department II, Cangzhou People's Hospital, Cangzhou, Hebei, 061000, China.
- 3. Oncology Department I, Hebei Chest Hospital, Shijiazhuang, Hebei, 050041, China.
- 4. Medical Science, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China; Jiangyin Jianhui Biotechnology Co., Ltd, Jiangyin, Jiangsu, 214431, China.
- 5. Medical Department, Baoding First Central Hospital, Baoding, Hebei, 071000, China.
- 6. Oncology Department III, Cangzhou People's Hospital, Cangzhou, Hebei, 061000, China.
- 7. Respiratory Medicine Department, Hebei Chest Hospital, Shijiazhuang, Hebei, 050041, China; Hebei Provincial Key Laboratory of Pulmonary Disease, Shijiazhuang, 050000, China. Electronic address: [email protected].
- 8. Department of Oncology, Graduate School, Hebei Medical University, Shijiazhuang, Hebei, 050011, China; Hebei Provincial Key Laboratory of Pulmonary Disease, Shijiazhuang, 050000, China; Oncology Department, Hebei Chest Hospital, Shijiazhuang, Hebei, 050041, China. Electronic address: [email protected].
Lung adenocarcinoma (LUAD) is a leading cause of cancer-related death worldwide. Immunotherapies that overcome tumor immune evasion have emerged as promising strategies. GFPT1, the rate-limiting enzyme of the hexosamine biosynthetic pathway, is commonly dysregulated in malignancies. The aim of this work is to investigate the functional significance and molecular basis of GFPT1 in immune escape of LUAD. GFPT1 expression was evaluated through integrated bioinformatic analysis and validation in clinical specimens. Functional assays were employed to assess tumor cell-mediated immune evasion. Mmechanistic investigations were supported by molecular assays and in vivo models. We demonstrated that elevated GFPT1 expression in LUAD promotes immune escape of tumor cells. Mechanically, GFPT1 stabilized the expression of MYC by O-GlcNAcylation of MYC, thereby contributing to LUAD progression. Overall, this study revealed the promoting effect of GFPT1 on the immune escape of LUAD, which provided new therapeutic targets for the immunotherapy of LUAD.