The MHC Class-I Transactivator NLRC5: Implications to Cancer Immunology and Potential Applications to Cancer Immunotherapy
The immune system constantly monitors the emergence of cancerous cells and eliminates them. CD8<sup>+</sup> cytotoxic T lymphocytes (CTLs), which kill tumor cells and provide antitumor immunity, select their targets by recognizing tumor antigenic peptides presented by MHC class-I (MHC-I)...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-02-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/4/1964 |
| _version_ | 1797396291766976512 |
|---|---|
| author | Akhil Shukla Maryse Cloutier Madanraj Appiya Santharam Sheela Ramanathan Subburaj Ilangumaran |
| author_facet | Akhil Shukla Maryse Cloutier Madanraj Appiya Santharam Sheela Ramanathan Subburaj Ilangumaran |
| author_sort | Akhil Shukla |
| collection | DOAJ |
| description | The immune system constantly monitors the emergence of cancerous cells and eliminates them. CD8<sup>+</sup> cytotoxic T lymphocytes (CTLs), which kill tumor cells and provide antitumor immunity, select their targets by recognizing tumor antigenic peptides presented by MHC class-I (MHC-I) molecules. Cancer cells circumvent immune surveillance using diverse strategies. A key mechanism of cancer immune evasion is downregulation of MHC-I and key proteins of the antigen processing and presentation machinery (APM). Even though impaired MHC-I expression in cancers is well-known, reversing the MHC-I defects remains the least advanced area of tumor immunology. The discoveries that NLRC5 is the key transcriptional activator of MHC-I and APM genes, and genetic lesions and epigenetic modifications of <i>NLRC5</i> are the most common cause of MHC-I defects in cancers, have raised the hopes for restoring MHC-I expression. Here, we provide an overview of cancer immunity mediated by CD8<sup>+</sup> T cells and the functions of NLRC5 in MHC-I antigen presentation pathways. We describe the impressive advances made in understanding the regulation of NLRC5 expression, the data supporting the antitumor functions of NLRC5 and a few reports that argue for a pro-tumorigenic role. Finally, we explore the possible avenues of exploiting NLRC5 for cancer immunotherapy. |
| first_indexed | 2024-03-09T00:49:12Z |
| format | Article |
| id | doaj.art-081a94360a5c42b7946f93b398a7e942 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T00:49:12Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-081a94360a5c42b7946f93b398a7e9422023-12-11T17:18:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01224196410.3390/ijms22041964The MHC Class-I Transactivator NLRC5: Implications to Cancer Immunology and Potential Applications to Cancer ImmunotherapyAkhil Shukla0Maryse Cloutier1Madanraj Appiya Santharam2Sheela Ramanathan3Subburaj Ilangumaran4Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, CanadaDepartment of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, CanadaDepartment of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, CanadaDepartment of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, CanadaDepartment of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, CanadaThe immune system constantly monitors the emergence of cancerous cells and eliminates them. CD8<sup>+</sup> cytotoxic T lymphocytes (CTLs), which kill tumor cells and provide antitumor immunity, select their targets by recognizing tumor antigenic peptides presented by MHC class-I (MHC-I) molecules. Cancer cells circumvent immune surveillance using diverse strategies. A key mechanism of cancer immune evasion is downregulation of MHC-I and key proteins of the antigen processing and presentation machinery (APM). Even though impaired MHC-I expression in cancers is well-known, reversing the MHC-I defects remains the least advanced area of tumor immunology. The discoveries that NLRC5 is the key transcriptional activator of MHC-I and APM genes, and genetic lesions and epigenetic modifications of <i>NLRC5</i> are the most common cause of MHC-I defects in cancers, have raised the hopes for restoring MHC-I expression. Here, we provide an overview of cancer immunity mediated by CD8<sup>+</sup> T cells and the functions of NLRC5 in MHC-I antigen presentation pathways. We describe the impressive advances made in understanding the regulation of NLRC5 expression, the data supporting the antitumor functions of NLRC5 and a few reports that argue for a pro-tumorigenic role. Finally, we explore the possible avenues of exploiting NLRC5 for cancer immunotherapy.https://www.mdpi.com/1422-0067/22/4/1964NLRC5MHC-Icancer immunotherapy |
| spellingShingle | Akhil Shukla Maryse Cloutier Madanraj Appiya Santharam Sheela Ramanathan Subburaj Ilangumaran The MHC Class-I Transactivator NLRC5: Implications to Cancer Immunology and Potential Applications to Cancer Immunotherapy International Journal of Molecular Sciences NLRC5 MHC-I cancer immunotherapy |
| title | The MHC Class-I Transactivator NLRC5: Implications to Cancer Immunology and Potential Applications to Cancer Immunotherapy |
| title_full | The MHC Class-I Transactivator NLRC5: Implications to Cancer Immunology and Potential Applications to Cancer Immunotherapy |
| title_fullStr | The MHC Class-I Transactivator NLRC5: Implications to Cancer Immunology and Potential Applications to Cancer Immunotherapy |
| title_full_unstemmed | The MHC Class-I Transactivator NLRC5: Implications to Cancer Immunology and Potential Applications to Cancer Immunotherapy |
| title_short | The MHC Class-I Transactivator NLRC5: Implications to Cancer Immunology and Potential Applications to Cancer Immunotherapy |
| title_sort | mhc class i transactivator nlrc5 implications to cancer immunology and potential applications to cancer immunotherapy |
| topic | NLRC5 MHC-I cancer immunotherapy |
| url | https://www.mdpi.com/1422-0067/22/4/1964 |
| work_keys_str_mv | AT akhilshukla themhcclassitransactivatornlrc5implicationstocancerimmunologyandpotentialapplicationstocancerimmunotherapy AT marysecloutier themhcclassitransactivatornlrc5implicationstocancerimmunologyandpotentialapplicationstocancerimmunotherapy AT madanrajappiyasantharam themhcclassitransactivatornlrc5implicationstocancerimmunologyandpotentialapplicationstocancerimmunotherapy AT sheelaramanathan themhcclassitransactivatornlrc5implicationstocancerimmunologyandpotentialapplicationstocancerimmunotherapy AT subburajilangumaran themhcclassitransactivatornlrc5implicationstocancerimmunologyandpotentialapplicationstocancerimmunotherapy AT akhilshukla mhcclassitransactivatornlrc5implicationstocancerimmunologyandpotentialapplicationstocancerimmunotherapy AT marysecloutier mhcclassitransactivatornlrc5implicationstocancerimmunologyandpotentialapplicationstocancerimmunotherapy AT madanrajappiyasantharam mhcclassitransactivatornlrc5implicationstocancerimmunologyandpotentialapplicationstocancerimmunotherapy AT sheelaramanathan mhcclassitransactivatornlrc5implicationstocancerimmunologyandpotentialapplicationstocancerimmunotherapy AT subburajilangumaran mhcclassitransactivatornlrc5implicationstocancerimmunologyandpotentialapplicationstocancerimmunotherapy |