Università della Svizzera italiana

The tim-3-galectin-9 secretory pathway is involved in the immune escape of human acute myeloid leukemia cells

Gonçalves Silva, Isabel ; Yasinska, Inna M. ; Sakhnevych, Svetlana S. ; Fiedler, Walter ; Wellbrock, Jasmin ; Bardelli, Marco ; Varani, Luca ; Hussain, Rohanah ; Siligardi, Giulio ; Ceccone, Giacomo ; Berger, Steffen M. ; Ushkaryov, Yuri A. ; Gibbs, Bernhard F. ; Fasler-Kan, Elizaveta ; Sumbayev, Vadim V.

In: Ebiomedicine, 2017, vol. 22, p. 44-57

Acute myeloid leukemia (AML) is a severe and often fatal systemic malignancy. Malignant cells are capable of escaping host immune surveillance by inactivating cytotoxic lymphoid cells. In this work we discovered a fundamental molecular pathway, which includes ligand-dependent activation of ectopically expressed latrophilin 1 and possibly other G-protein coupled receptors leading to increased...

Università della Svizzera italiana

The Tim-3-Galectin-9 Pathway and Its Regulatory Mechanisms in Human Breast Cancer

Yasinska, Inna M. ; Sakhnevych, Svetlana S. ; Pavlova, Ludmila ; Hansen Selnø, Anette Teo ; Teuscher Abeleira, Ana Maria ; Benlaouer, Ouafa ; Gonçalves Silva, Isabel ; Mosimann, Marianne ; Varani, Luca ; Bardelli, Marco ; Hussain, Rohanah ; Siligardi, Giuliano ; Cholewa, Dietmar ; Berger, Steffen M. ; Gibbs, Bernhard F. ; Ushkaryov, Yuri A. ; Fasler-Kan, Elizaveta ; Klenova, Elena ; Sumbayev, Vadim V.

In: Frontiers in immunology, 2019, vol. 10, p. 1594

Human cancer cells operate a variety of effective molecular and signaling mechanisms which allow them to escape host immune surveillance and thus progress the disease. We have recently reported that the immune receptor Tim-3 and its natural ligand galectin-9 are involved in the immune escape of human acute myeloid leukemia (AML) cells. These cells use the neuronal receptor latrophilin 1...

Università della Svizzera italiana

Differential expression and biochemical activity of the immune receptor Tim-3 in healthy and malignant human myeloid cells

Gonçalves Silva, Isabel ; Gibbs, Bernhard F. ; Bardelli, Marco ; Varani, Luca ; Sumbayev, Vadim V.

In: Oncotarget, 2015, vol. 6, no. 32, p. 33823-33833

The T cell immunoglobulin and mucin domain 3 (Tim-3) is a plasma membrane-associated receptor which is involved in a variety of biological responses in human immune cells. It is highly expressed in most acute myeloid leukaemia (AML) cells and therefore may serve as a possible target for AML therapy. However, its biochemical activities in primary human AML cells remain unclear. We therefore...

Università della Svizzera italiana

A bispecific immunotweezer prevents soluble PrP oligomers and abolishes prion toxicity

Bardelli, Marco ; Frontzek, Karl ; Simonelli, Luca ; Hornemann, Simone ; Pedotti, Mattia ; Mazzola, Federica ; Carta, Manfredi ; Eckhardt, Valeria ; D’Antuono, Rocco ; Virgilio, Tommaso ; González, Santiago F. ; Aguzzi, Adriano ; Varani, Luca

In: Plos pathogens, 2018, vol. 14, no. 10, p. e1007335

Antibodies to the prion protein, PrP, represent a promising therapeutic approach against prion diseases but the neurotoxicity of certain anti-PrP antibodies has caused concern. Here we describe scPOM-bi, a bispecific antibody designed to function as a molecular prion tweezer. scPOM-bi combines the complementarity-determining regions of the neurotoxic antibody POM1 and the neuroprotective...