EGC enhances tumor antigen presentation and CD8+ T cell-mediated antitumor immunity via targeting oncoprotein SND1.
Cancer Lett
; 592: 216934, 2024 Jun 28.
Article
em En
| MEDLINE
| ID: mdl-38710299
ABSTRACT
The Staphylococcal nuclease and Tudor domain containing 1 (SND1) has been identified as an oncoprotein. Our previous study demonstrated that SND1 impedes the major histocompatibility complex class I (MHC-I) assembly by hijacking the nascent heavy chain of MHC-I to endoplasmic reticulum-associated degradation. Herein, we aimed to identify inhibitors to block SND1-MHC-I binding, to facilitate the MHC-I presentation and tumor immunotherapy. Our findings validated the importance of the K490-containing sites in SND1-MHC-I complex. Through structure-based virtual screening and docking analysis, (-)-Epigallocatechin (EGC) exhibited the highest docking score to prevent the binding of MHC-I to SND1 by altering the spatial conformation of SND1. Additionally, EGC treatment resulted in increased expression levels of membrane-presented MHC-I in tumor cells. The C57BL/6J murine orthotopic melanoma model validated that EGC increases infiltration and activity of CD8+ T cells in both the tumor and spleen. Furthermore, the combination of EGC with programmed death-1 (PD-1) antibody demonstrated a superior antitumor effect. In summary, we identified EGC as a novel inhibitor of SND1-MHC-I interaction, prompting MHC-I presentation to improve CD8+ T cell response within the tumor microenvironment. This discovery presents a promising immunotherapeutic candidate for tumors.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Catequina
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Apresentação de Antígeno
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Linfócitos T CD8-Positivos
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Endonucleases
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Camundongos Endogâmicos C57BL
Limite:
Animals
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Humans
Idioma:
En
Revista:
Cancer Lett
Ano de publicação:
2024
Tipo de documento:
Article