Restoration of MHC-I on Tumor Cells by Fhit Transfection Promotes Immune Rejection and Acts as an Individualized Immunotherapeutic Vaccine
The capacity of cytotoxic-T lymphocytes to recognize and destroy tumor cells depends on the surface expression by tumor cells of MHC class I molecules loaded with tumor antigen peptides. Loss of MHC-I expression is the most frequent mechanism by which tumor cells evade the immune response. The resto...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/6/1563 |
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| author | María Pulido Virginia Chamorro Irene Romero Ignacio Algarra Alba S-Montalvo Antonia Collado Federico Garrido Angel M. Garcia-Lora |
| author_facet | María Pulido Virginia Chamorro Irene Romero Ignacio Algarra Alba S-Montalvo Antonia Collado Federico Garrido Angel M. Garcia-Lora |
| author_sort | María Pulido |
| collection | DOAJ |
| description | The capacity of cytotoxic-T lymphocytes to recognize and destroy tumor cells depends on the surface expression by tumor cells of MHC class I molecules loaded with tumor antigen peptides. Loss of MHC-I expression is the most frequent mechanism by which tumor cells evade the immune response. The restoration of MHC-I expression in cancer cells is crucial to enhance their immune destruction, especially in response to cancer immunotherapy. Using mouse models, we recovered MHC-I expression in the MHC-I negative tumor cell lines and analyzed their oncological and immunological profile. Fhit gene transfection induces the restoration of MHC-I expression in highly oncogenic MHC-I-negative murine tumor cell lines and genes of the IFN-γ transduction signal pathway are involved. Fhit-transfected tumor cells proved highly immunogenic, being rejected by a T lymphocyte-mediated immune response. Strikingly, this immune rejection was more frequent in females than in males. The immune response generated protected hosts against the tumor growth of non-transfected cells and against other tumor cells in our murine tumor model. Finally, we also observed a direct correlation between FHIT expression and HLA-I surface expression in human breast tumors. Recovery of Fhit expression on MHC class I negative tumor cells may be a useful immunotherapeutic strategy and may even act as an individualized immunotherapeutic vaccine. |
| first_indexed | 2024-03-10T19:12:34Z |
| format | Article |
| id | doaj.art-e558bb0d28ac44559897d9bdae1c0534 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T19:12:34Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-e558bb0d28ac44559897d9bdae1c05342023-11-20T03:41:16ZengMDPI AGCancers2072-66942020-06-01126156310.3390/cancers12061563Restoration of MHC-I on Tumor Cells by Fhit Transfection Promotes Immune Rejection and Acts as an Individualized Immunotherapeutic VaccineMaría Pulido0Virginia Chamorro1Irene Romero2Ignacio Algarra3Alba S-Montalvo4Antonia Collado5Federico Garrido6Angel M. Garcia-Lora7Servicio de Análisis Clínicos e Inmunología, UGC Laboratorio Clínico, Hospital Universitario Virgen de las Nieves, Av. de las Fuerzas Armadas 2, 18014 Granada, SpainServicio de Análisis Clínicos e Inmunología, UGC Laboratorio Clínico, Hospital Universitario Virgen de las Nieves, Av. de las Fuerzas Armadas 2, 18014 Granada, SpainUGC Laboratorios, Complejo Hospitalario de Jaén, 23007 Jaén, SpainDepartamento de Ciencias de la Salud, Universidad de Jaén, 23071 Jaén, SpainServicio de Análisis Clínicos e Inmunología, UGC Laboratorio Clínico, Hospital Universitario Virgen de las Nieves, Av. de las Fuerzas Armadas 2, 18014 Granada, SpainUnidad de Biobanco, Hospital Universitario Virgen de las Nieves, 18014 Granada, SpainServicio de Análisis Clínicos e Inmunología, UGC Laboratorio Clínico, Hospital Universitario Virgen de las Nieves, Av. de las Fuerzas Armadas 2, 18014 Granada, SpainServicio de Análisis Clínicos e Inmunología, UGC Laboratorio Clínico, Hospital Universitario Virgen de las Nieves, Av. de las Fuerzas Armadas 2, 18014 Granada, SpainThe capacity of cytotoxic-T lymphocytes to recognize and destroy tumor cells depends on the surface expression by tumor cells of MHC class I molecules loaded with tumor antigen peptides. Loss of MHC-I expression is the most frequent mechanism by which tumor cells evade the immune response. The restoration of MHC-I expression in cancer cells is crucial to enhance their immune destruction, especially in response to cancer immunotherapy. Using mouse models, we recovered MHC-I expression in the MHC-I negative tumor cell lines and analyzed their oncological and immunological profile. Fhit gene transfection induces the restoration of MHC-I expression in highly oncogenic MHC-I-negative murine tumor cell lines and genes of the IFN-γ transduction signal pathway are involved. Fhit-transfected tumor cells proved highly immunogenic, being rejected by a T lymphocyte-mediated immune response. Strikingly, this immune rejection was more frequent in females than in males. The immune response generated protected hosts against the tumor growth of non-transfected cells and against other tumor cells in our murine tumor model. Finally, we also observed a direct correlation between FHIT expression and HLA-I surface expression in human breast tumors. Recovery of Fhit expression on MHC class I negative tumor cells may be a useful immunotherapeutic strategy and may even act as an individualized immunotherapeutic vaccine.https://www.mdpi.com/2072-6694/12/6/1563MHC-I restorationFhitantitumor immunityimmune profilecytotoxic T lymphocytesimmunotherapy |
| spellingShingle | María Pulido Virginia Chamorro Irene Romero Ignacio Algarra Alba S-Montalvo Antonia Collado Federico Garrido Angel M. Garcia-Lora Restoration of MHC-I on Tumor Cells by Fhit Transfection Promotes Immune Rejection and Acts as an Individualized Immunotherapeutic Vaccine Cancers MHC-I restoration Fhit antitumor immunity immune profile cytotoxic T lymphocytes immunotherapy |
| title | Restoration of MHC-I on Tumor Cells by Fhit Transfection Promotes Immune Rejection and Acts as an Individualized Immunotherapeutic Vaccine |
| title_full | Restoration of MHC-I on Tumor Cells by Fhit Transfection Promotes Immune Rejection and Acts as an Individualized Immunotherapeutic Vaccine |
| title_fullStr | Restoration of MHC-I on Tumor Cells by Fhit Transfection Promotes Immune Rejection and Acts as an Individualized Immunotherapeutic Vaccine |
| title_full_unstemmed | Restoration of MHC-I on Tumor Cells by Fhit Transfection Promotes Immune Rejection and Acts as an Individualized Immunotherapeutic Vaccine |
| title_short | Restoration of MHC-I on Tumor Cells by Fhit Transfection Promotes Immune Rejection and Acts as an Individualized Immunotherapeutic Vaccine |
| title_sort | restoration of mhc i on tumor cells by fhit transfection promotes immune rejection and acts as an individualized immunotherapeutic vaccine |
| topic | MHC-I restoration Fhit antitumor immunity immune profile cytotoxic T lymphocytes immunotherapy |
| url | https://www.mdpi.com/2072-6694/12/6/1563 |
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