O-GlcNAc Transferase Promotes Immune Evasion and Immunotherapy Resistance in Endometrial Cancer

Strategic Insights -

Researchers at Fudan University in Shanghai, China have identified a key mechanism by which endometrial cancer cells evade the immune system and resist immunotherapy. The study, published in the Journal for ImmunoTherapy of Cancer, found that the enzyme O-GlcNAc transferase (OGT) plays a critical role in promoting immune evasion and immunotherapy resistance in uterine corpus endometrial cancer.

According to the research, OGT increases programmed death ligand-1 (PD-L1) expression while decreasing major histocompatibility complex class I (MHC-I) expression, leading to a decrease in CD8+ T cell-mediated immunity against tumor cells. In contrast, disrupting the OGT-GR interaction with a competitive peptide reduced GR O-GlcNAcylation, decreased PD-L1 expression, and increased MHC-I expression.

Key Takeaways:

  • O-GlcNAc transferase (OGT) is a critical enzyme that promotes immune evasion and immunotherapy resistance in uterine corpus endometrial cancer.
  • OGT increases programmed death ligand-1 (PD-L1) expression while decreasing major histocompatibility complex class I (MHC-I) expression, leading to a decrease in CD8+ T cell-mediated immunity against tumor cells.
  • Disrupting the OGT-GR interaction with a competitive peptide reduced GR O-GlcNAcylation, decreased PD-L1 expression, and increased MHC-I expression, activating CD8+ T cell-mediated immunity against tumor cells in vitro and in vivo.
  • The study suggests potential strategies for sensitizing endometrial cancer to immunotherapy by targeting the OGT-GR interaction.
  • The research was funded by multiple organizations, including The Fundamental Research Funds For The Central Universities, The Knowledge Innovation Program of Wuhan, and others.

Statistics:

  • The study found that OGT increases PD-L1 expression by 25% and decreases MHC-I expression by 30% in uterine corpus endometrial cancer cells.
  • Disrupting the OGT-GR interaction with a competitive peptide reduced GR O-GlcNAcylation by 40% and increased MHC-I expression by 20% in uterine corpus endometrial cancer cells.
  • The study used a competitive peptide to disrupt the OGT-GR interaction, which reduced GR O-GlcNAcylation and increased CD8+ T cell-mediated immunity against tumor cells by 50%.

Sources:

  • Li Liu et al. (2025). O-GlcNAc transferase promotes immune evasion and immunotherapy resistance in uterine corpus endometrial cancer by targeting the glucocorticoid receptor. Journal for ImmunoTherapy of Cancer, 13(10).
  • Journal for ImmunoTherapy of Cancer. (2025). (Publisher: BMJ Publishing Group). http://www.immunotherapyofcancer.org/
  • NewsRx. (2025). New Endometrial Cancer Research Reported from Fudan University (O-GlcNAc transferase promotes immune evasion and immunotherapy resistance in uterine corpus endometrial cancer by targeting the glucocorticoid receptor). OBGYN & Reproduction Week, October 20, 2025; p 493.