Contributors: 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.
نبذة مختصرة : 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
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