Receptor ligand interactions in immune responses to cancer and viruses

HReyburn

 

Hugh Reyburn

Group Leader

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Research summary

Current research in the laboratory addresses various issues related to the biology of NK cells and in particular the receptor NKG2D. We have a longstanding interest in studying the interactions between viruses and cells of the immune system as a strategy to gain insight into functionally important features of the immune system.

 

Publications

 

López-Cobo S, Pieper N, Campos-Silva C, García-Cuesta EM, Reyburn HT, Paschen A, Valés-Gómez M. Impaired NK cell recognition of vemurafenib-treated melanoma cells is overcome by simultaneous application of histone deacetylase inhibitors. Oncoimmunology. 2017 Nov 6;7(2):e1392426

Blázquez-Moreno A, Pérez-Portilla A, Agúndez-Llaca M, Dukovska D, Valés-Gómez M, Aydogmus C, Ikinciogullari A, Regueiro JR, Reyburn HT. Analysis of the recovery of CD247 expression in a PID patient: insights into the spontaneous repair of defective genes.Analysis of the recovery of CD247 expression in a PID patient: insights into the spontaneous repair of defective genes. Blood. 2017 Sep 7;130(10):1205-1208.

Blázquez-Moreno A, Park S, Im W, Call MJ, Call ME, Reyburn HT. Transmembrane features governing Fc receptor CD16A assembly with CD16A signaling adaptor molecules. Proc Natl Acad Sci U S A. 2017 Jul 11;114(28):E5645-E5654.

García-Cuesta EM, Esteso G, Ashiru O, López-Cobo S, Álvarez-Maestro M, Linares A, Ho MM, Martínez-Piñeiro L, T Reyburn H, Valés-Gómez M. Characterization of a human anti-tumoral NK cell population expanded after BCG treatment of leukocytes. Oncoimmunology. 2017 Feb 21;6(4):e1293212.

Romera-Cárdenas G, Thomas LM, Lopez-Cobo S, García-Cuesta EM, Long EO, Reyburn HT. Ionomycin Treatment Renders NK Cells Hyporesponsive. PLoS One 2016; 11: e0150998

Valés-Gómez M, Esteso G, Aydogmus C, Blázquez-Moreno A, Marín AV, Briones AC, Garcillán B, García-Cuesta EM, López Cobo S, Haskologlu S, Moraru M, Cipe F, Dobbs K, Dogu F, Parolini S, Notarangelo LD, Vilches C, Recio MJ, Regueiro JR, Ikinciogullari A, Reyburn HT. Natural killer cell hyporesponsiveness and impaired development in a CD247-deficient patient. J Allergy Clin Immunol 2016; 137:942-5

 

figuraReyburnWe study the interactions between pathogens and cells of the immune system to gain insight into functionally important features of the immune system, with the objective of applying this knowledge to studies of human disease.

The main research project is the identification of genes expressed by tumour cells and cells infected by viruses whose expression is associated with activation of NK cell cytotoxicity and cytokine secretion. We also study NK receptors that modulate lymphocyte activation, in particular the cell biology of these receptors, to understand their regulated expression and function. Recently we begun to study patients with primary T cell immunodeficiencies and have identified defects in NK cell development and function as well as aberrant expression of NK receptors on the defective T cells of these patients.

1. We showed that the shedding of molecules such as MICA and ICAM-1 is increased after HCMV infection both in vitro and in vivo. This phenomenon depends on increased activity of the metalloproteases ADAM17 and MMP14 due to decreased expression of the endogenous inhibitor of metalloproteases TIMP3. Assay of the sheddase activity of ADAM17 may be of use as a biomarker in patients at risk of developing CMV disease.

2. We discovered that innate immune recognition of double-stranded RNA produced during viral infection plays a key role in the induction of NKG2D ligand expression. These data suggest interesting parallels between the production of type I interferons and the induction of expression of NKG2D ligands. We identified proteins in both vaccinia virus and influenza virus whose expression markedly reduces the induction of both IFN-β and NKG2D ligands after infection.

3. Our recent analyses of patients with primary immunodeficiency diseases (PID) characterised by T cell lymphopaenia suggest defects other than simply the absence of T cell function. Specifically, the NK cells of these patients, although normal in number, were immature. These observations raise the exciting hypothesis that disruption of the normal crosstalk between immune cells can negatively affect the differentiation and function of the remaining cells of the immune system, and so contribute to the spectrum of pathology in these patients.

 

 grupoReyburnRed 

Name
Position
Contact
Hugh Reyburn Principal investigator
Daniela Dukovska Predoctoral scientist
Miriam Agúndez Llaca Predoctoral scientist
Alfonso Blázquez Moreno Predoctoral scientist
Ruth Gómez-Caro Gil Predoctoral scientist

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