Pulido, MaríaChamorro, VirginiaRomero, IreneAlgarra, IgnacioS-Montalvo, AlbaCollado, AntoniaGarrido, FedericoGarcia-Lora, Angel M.2022-09-232022-09-232020-06-12Pulido M, Chamorro V, Romero I, Algarra I, S-Montalvo A, Collado A, et al. Restoration of MHC-I on Tumor Cells by Fhit Transfection Promotes Immune Rejection and Acts as an Individualized Immunotherapeutic Vaccine. Cancers. 2020 Jun 12;12(6):1563http://hdl.handle.net/10668/4127The 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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/MHC-I restorationFhitAntitumor immunityImmune profileCytotoxic t lymphocytesImmunotherapyVaccineTumor cellsMiceLinfocitos t citotóxicosVacunaRatonesMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Antigens, Surface::Histocompatibility Antigens::Histocompatibility Antigens Class IMedical Subject Headings::Chemicals and Drugs::Biological Factors::Antigens::Antigens, NeoplasmMedical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Cytokine-Induced Killer Cells::T-Lymphocytes, CytotoxicMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, TumorMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Gene Transfer Techniques::TransfectionMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::ImmunotherapyMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Signal TransductionMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Breast NeoplasmsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::PeptidesMedical Subject Headings::Chemicals and Drugs::Complex Mixtures::Biological Products::Vaccinesresearch article32545680open access10.3390/cancers120615632072-6694PMC7352176