MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy
1
Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands
2
Princess Máxima Center for Pediatric Oncology, Utrecht University, 3584 CS Utrecht, The Netherlands
*
Author to whom correspondence should be addressed.
†
These authors have contributed equally to this work.
Cancers 2020, 12(7), 1760; https://doi.org/10.3390/cancers12071760
Received: 11 June 2020
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Revised: 29 June 2020
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Accepted: 29 June 2020
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Published: 2 July 2020
(This article belongs to the Special Issue Cancer-Induced Immune Suppression: An Achilles’ Heel of Current Immunotherapy)
In recent years, major advances have been made in cancer immunotherapy. This has led to significant improvement in prognosis of cancer patients, especially in the hematological setting. Nonetheless, translation of these successes to solid tumors was found difficult. One major mechanism through which solid tumors can avoid anti-tumor immunity is the downregulation of major histocompatibility complex class I (MHC-I), which causes reduced recognition by- and cytotoxicity of CD8+ T-cells. Downregulation of MHC-I has been described in 40–90% of human tumors, often correlating with worse prognosis. Epigenetic and (post-)transcriptional dysregulations relevant in the stabilization of NFkB, IRFs, and NLRC5 are often responsible for MHC-I downregulation in cancer. The intrinsic reversible nature of these dysregulations provides an opportunity to restore MHC-I expression and facilitate adaptive anti-tumor immunity. In this review, we provide an overview of the mechanisms underlying reversible MHC-I downregulation and describe potential strategies to counteract this reduction in MHC-I antigen presentation in cancer.
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Keywords:
MHC-I downregulation; cancer immunotherapy; antigen presentation; tumor immunogenicity; adaptive immune involvement
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MDPI and ACS Style
Cornel, A.M.; Mimpen, I.L.; Nierkens, S. MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy. Cancers 2020, 12, 1760. https://doi.org/10.3390/cancers12071760
AMA Style
Cornel AM, Mimpen IL, Nierkens S. MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy. Cancers. 2020; 12(7):1760. https://doi.org/10.3390/cancers12071760
Chicago/Turabian StyleCornel, Annelisa M., Iris L. Mimpen, and Stefan Nierkens. 2020. "MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy" Cancers 12, no. 7: 1760. https://doi.org/10.3390/cancers12071760
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