EGC enhances tumor antigen presentation and CD8+ T cell-mediated antitumor immunity via targeting oncoprotein SND1

Xinxin Zhang1, Xiaoteng Cui2, Peiying Li1

  • 1Tianjin Key Laboratory of Cellular and Molecular Immunology, and Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin, China; The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin, China; State Key Laboratory of Experimental Hematology, Tianjin, China; Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Science, Tianjin Medical University, Tianjin, China.

Cancer Letters
|May 6, 2024
PubMed

Insights

We identified (-)-Epigallocatechin (EGC) as a novel inhibitor that blocks the oncoprotein SND1 from binding to MHC-I. This enhances tumor immunotherapy by improving T cell responses against cancer.

Area of Science:

  • Oncology
  • Immunology
  • Biochemistry

Background:

  • Staphylococcal nuclease and Tudor domain containing 1 (SND1) is an oncoprotein that hinders major histocompatibility complex class I (MHC-I) presentation.
  • SND1 targets MHC-I heavy chains for degradation, reducing cancer cells' ability to display antigens.

Purpose of the Study:

  • To identify inhibitors that disrupt the SND1-MHC-I interaction.
  • To enhance MHC-I presentation for improved tumor immunotherapy.

Main Methods:

  • Structure-based virtual screening and docking analysis identified potential inhibitors.
  • In vitro assays assessed the effect of inhibitors on MHC-I expression.
  • Murine melanoma models evaluated anti-tumor efficacy and T cell responses.
  • Combination therapy with PD-1 antibody was tested.

Main Results:

  • (-)-Epigallocatechin (EGC) showed high binding affinity, preventing SND1-MHC-I interaction by altering SND1 conformation.
  • EGC treatment increased membrane-bound MHC-I expression in tumor cells.
  • EGC enhanced CD8+ T cell infiltration and activity in tumors and spleens.
  • Combined EGC and PD-1 antibody treatment yielded superior anti-tumor effects.

Conclusions:

  • EGC is a novel inhibitor of the SND1-MHC-I interaction.
  • EGC enhances MHC-I presentation, boosting CD8+ T cell responses.
  • EGC represents a promising immunotherapeutic candidate for cancer treatment.

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