RT Journal Article
T1 Restoration of MHC-I on Tumor Cells by Fhit Transfection Promotes Immune Rejection and Acts as an Individualized Immunotherapeutic Vaccine.
A1 Pulido, María
A1 Chamorro, Virginia
A1 Romero, Irene
A1 Algarra, Ignacio
A1 S-Montalvo, Alba
A1 Collado, Antonia
A1 Garrido, Federico
A1 Garcia-Lora, Angel M
K1 Fhit
K1 MHC-I restoration
K1 antitumor immunity
K1 cytotoxic T lymphocytes
K1 immune profile
K1 immunotherapy
K1 vaccine
AB 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.
SN 2072-6694
YR 2020
FD 2020-06-12
LK https://hdl.handle.net/10668/28185
UL https://hdl.handle.net/10668/28185
LA en
DS RISalud
RD Apr 7, 2025