Restoration of MHC-I on Tumor Cells by Fhit Transfection Promotes Immune Rejection and Acts as an Individualized Immunotherapeutic Vaccine
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MHC-I restorationFhitAntitumor immunityImmune profileCytotoxic T lymphocytesImmunotherapyVaccines
Pulido, M., Chamorro, V., Romero, I., Algarra, I., Collado, A., Garrido, F., & Garcia-Lora, A. M. (2020). Restoration of MHC-I on Tumor Cells by Fhit Transfection Promotes Immune Rejection and Acts as an Individualized Immunotherapeutic Vaccine. Cancers, 12(6), 1563. [doi: 10.3390/cancers12061563]
SponsorshipFEDER 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
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.