RNA in exosomes from cancer cells subverts the immune system

2017 - 08 - 29

RNA in exosomes from cancer cells subverts the immune system

In chronic lymphocytic leukaemia (CLL), cancer cells are able to manipulate the surrounding cells to their own benefit by the release of exosomes, small vesicles filled with a cocktail of biomolecules. In a recent study published in the journal “Science Immunology”, scientists from the German Cancer Research Centre (DKFZ) in Heidelberg, together with collaborators from different German institutes and from LIH’s Department of Oncology, identified a non-coding RNA contained in exosomes that plays an important role in ensuring tumour growth.

CLL is a slowly progressing blood cancer mostly affecting people aged more than 50 that can only develop in a tumour-supportive microenvironment in which the immune response is suppressed. To create this environment, cancer cells manipulate surrounding monocytes and macrophages, bringing them to release cytokines that protect the tumour and to produce immunosuppressive molecules such as programmed cell death 1 ligand 1 (PD-L1).

In this study, the scientists identified a small non-coding Y RNA named hY4 that is very abundant in exosomes released by leukemic cells. They treated human and mice cultured monocytes and macrophages with CLL-derived exosomes, as well as with synthetic Y RNA. In both cases, the cells changed similarly to how they would in CLL patients, leading amongst other effects to the higher production of the immune inhibitor PD-L1. Further experiments showed that Y RNA can activate the immune receptor Toll-like receptor 7 (TLR7), which ultimately leads to more PD-L1. New treatment strategies could therefore be to target PD-L1 or TLR7.

Dr Franziska Haderk, first-author of the publication, spent three months in the “Tumour Stroma Interactions” research group of Dr Etienne Moussay and Dr Jérôme Paggetti at the Laboratory of Experimental Cancer Research in LIH’s Department of Oncology to acquire knowledge on techniques to prepare and analyse exosomes and to conduct part of the experiments. ‘Our group has a unique expertise in isolating and characterising exosomes from which collaborating research groups can benefit’, tell the two researchers.

Link to publication: Tumour-derived exosomes modulate PD-L1 expression in monocytes