Thermal- and oxidative stress cause enhanced release of NKG2D ligand-bearing immunosuppressive exosomes in leukemia-lymphoma T and B cells
(English)Article in journal (Other academic) Submitted
Immune evasion from NK surveillance related to inadequate NK-cell function has been suggested as an explanation to the high incidence of relapse and fatal outcome of many blood malignancies. Using Jurkat and Raji cell lines as a model we show that leukemia/lymphoma T and B cells constitutively secrete exosomes carrying MICA/B, ULBP1 and 2, ligands for the activating NK-cell receptor NKG2D. Acting as a decoy, the NKG2D ligand-bearing exosomes downregulate NKG2D receptor-mediated cytotoxicity and impair NK-cell function. Furthermore, we show that thermal and oxidative stress enhances the exosome secretion generating more soluble NKG2D ligands that aggravate the impairment of the cytotoxic response. Taken together, our results might partly explain the clinically observed NK-cell dysfunction in patients suffering from leukemia/lymphoma. The adverse effect of thermal and oxidative stress enhancing the release of immunosuppressive exosomes should be considered when cytostatic and hyperthermal anti-cancer therapies are designed.
exosomes, NKG2D, MIC/ULBP, leukemia/lymphoma, oxidative stress, thermal stress, hyperthermia
Research subject Immunology
IdentifiersURN: urn:nbn:se:umu:diva-37120OAI: oai:DiVA.org:umu-37120DiVA: diva2:357985