Centro Interdisciplinario de Neurociencia de Valparaíso
Laboratory of Molecular Sensors
Principal Investigator: Dr. Carlos González
Ph.D. in Biological Sciences, University of Havana, Cuba (2014).
Master degree in Biochemistry, mention Immunology, University of Havana, Cuba (2008)
Bachelor degree in Biochemistry, University of Havana, Cuba (2004)
Fax: (56)-(32)-250 8027
Address: Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias,
Universidad de Valparaíso. Gran Bretaña 1111. Playa Ancha, Valparaíso-Chile.
The tumor microenvironment is a major hurdle limiting the efficacy of cancer immunotherapy, since several mechanisms disable the function of anti-tumor T cells within this complex niche. The evidence demonstrates an increased infiltration of tumors with immune populations that inhibit T cell activation, cytokine release and cytotoxicity. Most of these immune populations also promote the proliferation of tumor cells, the vascularization of the tumor and the metastatic spreading. Furthermore, there is an impairment of the mechanisms of antigen presentation that are essential for both natural anti-tumor immune surveillance and anti-tumor vaccination. Another element contributing to immune dysfunction is the metabolism of tumor cells, which establishes a microenvironment with low pH and high levels of reactive oxygen species that limit not only the function of T cells but also their viability.
Interestingly, Hv1 proton channel is expressed in tumor cells where it is involved in the maintenance of intracellular pH and the acidification of the tumor microenvironment. The inhibition or absence of Hv1 proton channel reduces the migration and invasiveness of metastatic cell lines. Additionally, it has been described that Hv1 proton channel supports a long-term function of NADPH oxidase and the production of reactive oxygen species in different leukocytes, a critical function for phagocytic killing of pathogens, for the regulation of antigen processing and presentation and that is associated with the control of T cell activation. Of note, the generation of reactive oxygen species is increased within the tumor microenvironment promoting T cell suppression and inflammation. Thus, our project focuses in the study of the expression and functional role of Hv1 proton channel on tumor-infiltrating immune cells that contribute to tumor progression.
- Fernández A, Oliver L, Alvarez R, Fernández LE, Lee KP, Mesa C. Adjuvants and myeloid-derived suppressor cells: Enemies or allies in therapeutic cancer vaccination. Review. Human Vaccines and Immunotherapeutics. 2014; 10: 3251-3260.
- Fernández A, Oliver L, Alvarez R, Fernández LE, Mesa C. GM3-containing nanoparticles in immunosuppressed hosts: Effect on myeloid-derived suppressor cells. Review. World Journal of Immunology. 2014; 4:98.
- Fernández A, Oliver L, Alvarez R, Hernández A, Raymond J, Fernández LE, Mesa C. Very Small Size Proteoliposomes abrogate cross-presentation of tumor antigens by myeloid-derived suppressor cells and induce their differentiation to dendritic cells. Journal for ImmunoTherapy of Cancer. 2014; 2:5.
- Oliver L, Fernández A, Raymond J, López-Requena A, Fernández LE, Mesa C. Very small size proteoliposomes derived from Neisseria meningitidis: an effective adjuvant for antigen-specific cytotoxic T lymphocyte response stimulation under leukopenic conditions. Vaccine. 2012; 30:2963-2972.
- Fernández A, Mesa C, Marigo I, Dolcetti L, Clavell M, Oliver L, Fernández LE, Bronte V. Inhibition of tumor-induced myeloid-derived suppressor cell function by a nanoparticulated adjuvant. Journal of Immunology. 2011; 186:264-274.
- Marigo I, Bosio E, Solito S, Mesa C, Fernandez A, Dolcetti L, Ugel S, Sonda N, Bicciato S, Falisi E, Calabrese F, Basso G, Zanovello P, Cozzi E, Mandruzzato S, Bronte V. Tumor-induced tolerance and immune suppression depend on the C/EBPbeta transcription factor. Immunity. 2010; 32:790-802.
- Dolcetti, L., E. Peranzoni, S. Ugel, I. Marigo, A. Fernandez Gomez, C. Mesa, M. Geilich, G. Winkels, E. Traggiai, A. Casati, F. Grassi, and V. Bronte. Hierarchy of immunosuppressive strength among myeloid-derived suppressor cell subsets is determined by GM-CSF. European Journal of Immunology. 2010; 40:22-35.
- Mazorra Z, Mesa C, Fernández A, Fernández LE. Immunization with a GM3 ganglioside nanoparticulated vaccine confers an effector CD8+ T cells-mediated protection against melanoma B16 challenge. Cancer Immunology and Immunotherapy. 2008; 57:1771-80.
- De León J, Fernández A, Clavell M, Labrada M, Bebelagua Y, Mesa C, Fernández LE. Differential influence of the tumour-specific nonhuman sialic acid containing GM3 ganglioside on CD4+CD25- effector and naturally occurring CD4+CD25+ regulatory T cells function. International Immunology. 2008; 20:591-600.
- de Leon J, Fernandez A, Mesa C, Clavel M, Fernandez LE. Role of tumour-associated N-glycolylated variant of GM3 ganglioside in cancer progression: effect over CD4 expression on T cells. Cancer Immunology and Immunotherapy. 2006; 55:443-50.