Tumor-exosomes and leukocyte activation: an ambivalent crosstalk

ASML-exosomes bind to and are taken up by all leukocyte subpopulations in vivo and in vitro, uptake by CD11b+ leukocytes exceeding that by T and B cells. ASML-exosomes affect leukocyte proliferation via reduced CD44v6 up-regulation and lck, ZAP70 and ERK1,2 phosphorylation, which can be compensated by dendritic cells (DC). ASML-exosomes do not support Treg. Yet, impaired activation of anti-apoptotic signals is accompanied by slightly increased apoptosis susceptibility. IgM secretion is unaffected; NK and CTL activity are strengthened, ASML-exosomes co-operating with DC in CTL activation. ASML-exosomes transiently interfere with leukocyte migration by occupying migration-promoting receptors CD44, CD49d, CD62L and CD54 during binding/internalization.ASML-exosomes might well serve as adjuvant in immunotherapy as they support leukocyte effector functions and have only a minor impact on leukocyte activation, which can be overridden by DC. However, exosome-induced modulation of immune cells relies, at least in part, on exosome uptake and message transfer. This implies that depending on the individual tumor's exosome composition, exosomes may distinctly affect the immune system. Nonetheless, whether immunotherapy can profit from using tumor-exosomes as adjuvant can easily be settled beforehand in vitro.Exosomes, potent intercellular communicators that play a pivotal role in physiological and pathological processes [1] are found in all body fluids [2] and bind / are taken up by selected targets [3]. Exosomes contain function-competent proteins, mRNA and miRNA [1], which can severely affect the target cells [4,5]. These findings advocate for therapeutic use of exosomes, which is particularly appreciated in immunotherapy, as dendritic cell (DC)-exosomes, highly expressing MHCI, MHCII, CD80 and CD86, are fully equipped to initiate T cell activation [6,7].DC-exosomes being a promising means for immunotherapy [6,8], hope has been dampened by tumor-exosomes interfering with immun