Tumour-derived small extracellular vesicles contribute to the tumour progression through reshaping the systemic immune macroenvironment
Menée in vitro et à l'aide d'un modèle murin, cette étude met en évidence un mécanisme par lequel les petites vésicules extracellulaires issues des tumeurs contribuent à la progression tumorale en altérant la composition et la fonction du macro-environnement immunitaire
Background : Tumour-derived small extracellular vesicles (sEVs) play a crucial role in cancer immunomodulation. In addition to tumour immune microenvironment, the peripheral immune system also contributes significantly to cancer progression and is essential for anticancer immunity. However, a comprehensive definition of which and how peripheral immune lineages are regulated by tumour-derived sEVs during cancer development remains incomplete. Methods : In this study, we used mass cytometry with extensive antibody panels to comprehensively construct the systemic immune landscape in response to tumour development and tumour-derived sEVs. Results : Systemic immunity was dramatically altered by tumour growth and tumour-derived sEVs. Tumour-derived sEVs significantly and extensively affected immune cell population composition as well as intracellular pathways, resulting in an immunosuppressive peripheral and tumour immune microenvironment, characterised by increased myeloid-derived suppressor cells and decreased Ly6C+CD8 T cells. These sEVs largely promoted hematopoietic recovery and accelerate the differentiation towards myeloid-derived suppressor cells. The knockdown of Rab27a reduced sEV secretion from tumour cells and delayed tumour growth and metastasis in vivo. Conclusions : These results highlight that tumour-derived sEVs function as a bridge between peripheral immunity regulation and the tumour microenvironment, and contribute to cancer progression through altering the composition and function of the global immune macroenvironment.