Targeting the liver X receptor with dendrogenin A differentiates tumour cells to secrete immunogenic exosome‐enriched vesicles

Autor: Michel Record, Mehdi Attia, Kevin Carayon, Laly Pucheu, Julio Bunay, Régis Soulès, Silia Ayadi, Bruno Payré, Laure Perrin‐Cocon, Florence Bourgailh, Antonin Lamazière, Vincent Lotteau, Marc Poirot, Sandrine Silvente‐Poirot, Philippe de Medina
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Journal of Extracellular Vesicles, Vol 11, Iss 4, Pp n/a-n/a (2022)
Druh dokumentu: article
ISSN: 2001-3078
DOI: 10.1002/jev2.12211
Popis: Abstract Tumour cells are characterized by having lost their differentiation state. They constitutively secrete small extracellular vesicles (sEV) called exosomes when they come from late endosomes. Dendrogenin A (DDA) is an endogenous tumour suppressor cholesterol‐derived metabolite. It is a new class of ligand of the nuclear Liver X receptors (LXR) which regulate cholesterol homeostasis and immunity. We hypothesized that DDA, which induces tumour cell differentiation, inhibition of tumour growth and immune cell infiltration into tumours, could functionally modify sEV secreted by tumour cells. Here, we have shown that DDA differentiates tumour cells by acting on the LXRβ. This results in an increased production of sEV (DDA‐sEV) which includes exosomes. The DDA‐sEV secreted from DDA‐treated cells were characterized for their content and activity in comparison to sEV secreted from control cells (C‐sEV). DDA‐sEV were enriched, relatively to C‐sEV, in several proteins and lipids such as differentiation antigens, “eat‐me” signals, lipidated LC3 and the endosomal phospholipid bis(monoacylglycero)phosphate, which stimulates dendritic cell maturation and a Th1 T lymphocyte polarization. Moreover, DDA‐sEV inhibited the growth of tumours implanted into immunocompetent mice compared to control conditions. This study reveals a pharmacological control through a nuclear receptor of exosome‐enriched tumour sEV secretion, composition and immune function. Targeting the LXR may be a novel way to reprogram tumour cells and sEV to stimulate immunity against cancer.
Databáze: Directory of Open Access Journals
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