Restoration of MHC-I on Tumor Cells by Fhit Transfection Promotes Immune Rejection and Acts as an Individualized Immunotherapeutic Vaccine
| Autor: | Alba S-Montalvo, Federico Garrido, Antonia Collado, Angel M. Garcia-Lora, María Pulido, Irene Romero, Virginia Chamorro, Ignacio Algarra |
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| Přispěvatelé: | UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie, [Pulido,M, Chamorro,V, S-Montalvo,A, Garrido,F, Garcia-Lora,AM] Servicio de Análisis Clínicos e Inmunología, UGC Laboratorio Clínico, Hospital Universitario Virgen de las Nieves, Granada, Spain. [Pulido,M, Garcia-Lora,AM] Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain. [Romero,I] UGC Laboratorios, Complejo Hospitalario de Jaén, Jaén, Spain. [Algarra,I] Departamento de Ciencias de la Salud, Universidad de Jaén, Jaén, Spain. [Collado,A] Unidad de Biobanco, Hospital Universitario Virgen de las Nieves, Granada, Spain. [Garrido,F] Departamento de Bioquímica, Biología Molecular e Inmunología III, Universidad de Granada, Granada, Spain., This work was supported by grants cofinanced by FEDER funds (EU) from the Instituto de Salud Carlos III (PI12/02031, PI14/01978, PI15/00528, PI17/00197, PI19/01179, PT13/0010/0039 and PT17/0015/0041), Worldwide Cancer Research project 15-1166, Junta de Andalucía (Group CTS-143, CTS-3952, CVI-4740 grants). A.M.G.L. was supported by Contract I3-SNS from Junta de Andalucía and ISCIII, I. R. by Rio-Hortega Contract CM12/00033 from ISCIII, and M. P. by ibs.Granada Fellowship 496. |
| Rok vydání: | 2020 |
| Předmět: |
Anatomy::Cells::Cells
Cultured::Cell Line::Cell Line Tumor [Medical Subject Headings] 0301 basic medicine Cancer Research Ratones medicine.medical_treatment Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] Mice Chemicals and Drugs::Biological Factors::Antigens::Antigens Surface::Histocompatibility Antigens::Histocompatibility Antigens Class I [Medical Subject Headings] 0302 clinical medicine Cancer immunotherapy FHIT vaccine Organisms::Eukaryota::Animals [Medical Subject Headings] Analytical Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy [Medical Subject Headings] Cytotoxic T cell Chemicals and Drugs::Complex Mixtures::Biological Products::Vaccines [Medical Subject Headings] Vaccines biology Vacuna Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Signal Transduction [Medical Subject Headings] immune profile lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Tumor antigen Oncology 030220 oncology & carcinogenesis Linfocitos t citotóxicos immunotherapy antitumor immunity Check Tags::Male [Medical Subject Headings] chemical and pharmacologic phenomena Tumor cells cytotoxic T lymphocytes Major histocompatibility complex lcsh:RC254-282 Article MHC-I restoration 03 medical and health sciences Immune system MHC class I medicine Chemicals and Drugs::Amino Acids Peptides and Proteins::Peptides [Medical Subject Headings] Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings] Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes Mononuclear::Cytokine-Induced Killer Cells::T-Lymphocytes Cytotoxic [Medical Subject Headings] Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings] Fhit Immunotherapy Chemicals and Drugs::Biological Factors::Antigens::Antigens Neoplasm [Medical Subject Headings] 030104 developmental biology Cancer research biology.protein Analytical Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Gene Transfer Techniques::Transfection [Medical Subject Headings] |
| Zdroj: | Cancers Cancers, Vol. 12, no. 6, p. 1563 [1-23] (2020) Cancers, Vol 12, Iss 1563, p 1563 (2020) Digibug: Repositorio Institucional de la Universidad de Granada Universidad de Granada (UGR) Digibug. Repositorio Institucional de la Universidad de Granada instname Volume 12 Issue 6 |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers12061563 |
| Popis: | The authors thank I. Linares, V. Sanz, A.B. Rodriguez, A.I. Rodriguez and E. Arias for technical advice and R. Davies for editorial assistance. 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. FEDER funds (EU) from the Instituto de Salud Carlos III PI12/02031 PI14/01978 PI15/00528 PI17/00197 PI19/01179 PT13/0010/0039 PT17/0015/0041 Worldwide Cancer Research 15-1166 Junta de Andalucia CTS-143 CTS-3952 CVI-4740 Instituto de Salud Carlos III Rio-Hortega Contract from ISCIII CM12/00033 ibs.Granada Fellowship 496 |
| Databáze: | OpenAIRE |
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