1. Restoration of MHC-I on Tumor Cells by Fhit Transfection Promotes Immune Rejection and Acts as an Individualized Immunotherapeutic Vaccine
- Author
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Alba S-Montalvo, Federico Garrido, Antonia Collado, Angel M. Garcia-Lora, María Pulido, Irene Romero, Virginia Chamorro, Ignacio Algarra, 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., and 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.
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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] - Abstract
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
- Published
- 2020
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