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Immune MAL2-practice: breast cancer immunoevasion via MHC class I degradation
Devin Dersh, Jonathan W. Yewdell
Devin Dersh, Jonathan W. Yewdell
Published January 4, 2021
Citation Information: J Clin Invest. 2021;131(1):e144344. https://doi.org/10.1172/JCI144344.
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Commentary

Immune MAL2-practice: breast cancer immunoevasion via MHC class I degradation

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Abstract

The success of tumor immunotherapy, while partial, confirms the existence and importance of tumor immunosurveillance. CD8+ T cell recognition of tumor-specific peptides bound to MHC class I (MHC-I) molecules is central to this process. In this issue of the JCI, Fang, Wang, et al. describe a unique tumor immunoevasion strategy based on endocytosis and degradation of MHC-I complexes mediated by the trafficking factor MAL2. Notably, MAL2 expression was associated with poor prognosis of breast cancer, and its downregulation enhanced CD8+ T cell recognition of breast cancer in various experimental models. This work demonstrates that a deeper understanding of tumor interference with MHC-I stability and trafficking has considerable potential for enhancing immunotherapies.

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Devin Dersh, Jonathan W. Yewdell

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