MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer 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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/12/7/1760 |
| _version_ | 1797563539961937920 |
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| author | Annelisa M. Cornel Iris L. Mimpen Stefan Nierkens |
| author_facet | Annelisa M. Cornel Iris L. Mimpen Stefan Nierkens |
| author_sort | Annelisa M. Cornel |
| collection | DOAJ |
| description | 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<sup>+</sup> 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. |
| first_indexed | 2024-03-10T18:44:06Z |
| format | Article |
| id | doaj.art-f7b564c2c0ad4a92a467d73eb568b00a |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T18:44:06Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f7b564c2c0ad4a92a467d73eb568b00a2023-11-20T05:38:34ZengMDPI AGCancers2072-66942020-07-01127176010.3390/cancers12071760MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer ImmunotherapyAnnelisa M. Cornel0Iris L. Mimpen1Stefan Nierkens2Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The NetherlandsCenter for Translational Immunology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The NetherlandsCenter for Translational Immunology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The NetherlandsIn 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<sup>+</sup> 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.https://www.mdpi.com/2072-6694/12/7/1760MHC-I downregulationcancer immunotherapyantigen presentationtumor immunogenicityadaptive immune involvement |
| spellingShingle | Annelisa M. Cornel Iris L. Mimpen Stefan Nierkens MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy Cancers MHC-I downregulation cancer immunotherapy antigen presentation tumor immunogenicity adaptive immune involvement |
| title | MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy |
| title_full | MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy |
| title_fullStr | MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy |
| title_full_unstemmed | MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy |
| title_short | MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy |
| title_sort | mhc class i downregulation in cancer underlying mechanisms and potential targets for cancer immunotherapy |
| topic | MHC-I downregulation cancer immunotherapy antigen presentation tumor immunogenicity adaptive immune involvement |
| url | https://www.mdpi.com/2072-6694/12/7/1760 |
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