Tumour immune activation and evasion

MVales

 

Mar Valés Gómez

Group Leader

Contact

 

Research summary

Our group is interested in the molecular recognition of targets by Natural Killer (NK) cells, in particular, we study the interaction between NK receptors and its ligands and the functional consequences. In the last years, we have investigated the system of the activating receptor NKG2D, as its ligands provide a model of molecules that signal stress to the immune system. Analysing the cell surface expression regulation of NKG2D ligands, we have described the biological routes involved in the release of these proteins to the extracellular milieu: metalloproteases and extracellular vesicles (exosomes). Our long-term goal is to apply our results to biomedically relevant systems, mainly, cancer. For this purpose, we study the immune response towards cancer in two systems: bladder cancer and melanoma.

 

Publications

López-Cobo S, Pieper N, Campos-Silva C, García‐Cuesta EM, Reyburn HT, Paschen A and Valés-Gómez M. Impaired NK cell recognition of vemurafenib-treated melanoma cells is overcome by simultaneous application of histone deacetylase inhibitors. Oncoimmunology 2017;7(2):e1392426.

García-Cuesta EM, Esteso G, Ashiru O, López-Cobo S, Álvarez-Maestro M, Linares A, Ho M, Martínez-Piñeiro L, Reyburn HT and Valés-Gómez M. Characterisation of a human anti-tumoral NK cell population expanded after BCG treatment of leukocytes. Oncoimmunology 2017;6(4):e1293212

López-Cobo S, Campos-Silva C, Valés-Gómez M. Glycosyl-Phosphatidyl-Inositol (GPI)-Anchors and Metalloproteases: Their Roles in the Regulation of Exosome Composition and NKG2D-Mediated Immune Recognition. Front Cell Dev Biol, 4:97. 2016.

Valés-Gómez M. The Impact of Glycosyl-Phosphatidyl-Inositol Anchored MICA Alleles on Novel NKG2D-Based Therapies. Frontiers in Immunology 2015; 6:193

Ashiru O, López-Cobo S, Fernández-Messina L, Reyburn HT, Valés-Gómez M. A GPI anchor explains the unique biological features of the common KG2D-ligand allele MICA*008. Biochem J. 2013;454(2):295-302

 

 

 

Figure1ValesWe are interested on the modulation of the NK cell activation in the context of cancer and, currently, to follow this objective we study both in vitro models and patient samples ex-vivo. We use a range of biochemical, molecular and immunological techniques to understand the differentiation and proliferation events that occur in the NK cell compartment in the context of cancer and the changes provoked by therapies. For example, in the case of bladder cancer, we follow the treatment with BCG (Bacille Calmette-Guérin), while in melanoma, we study BRAF inhibitors. The group is interested in describing the detailed phenotype of NK cells with anti-tumoral capacities and the factors required for their differentiation. In parallel, we study immune modulating molecules, such as the ligands for the activating receptor NKG2D, secreted by tumours, either soluble or as part of extracellular vesicles, like exosomes. In this context, we are also interested in developing exosome-based tools for immune modulation and technologies that will permit easier detection of exosomal biomarkers in cancer. We have started to establish collaborations in order to pursue this goal: with clinicians to have access to samples, with researchers and technological partners to develop the tools and we are part of a new Spanish network for research in extracellular vesicles.

 

 vales group 2018 

Name
Position
Contact
Mar Valés Gómez Principal investigator
Gloria Esteso Tornero Postdoctoral scientist
Carmen Campos Silva Predoctoral scientist
Maren K. Kramer Predoctoral scientist
Adrián Fernández Martín Visiting student

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