Abstract B19: Suppression of CD8+ T-cell functions by melanoma cell-derived exosomes captured from plasma of patients with melanoma

Abstract

Abstract Exosomes, virus-sized (30-150nm) vesicles, derived from the endocytic compartment of parent cells, are produced by all cells and are present in all body fluids. Melanoma patients’ plasma contains exosomes produced by normal and malignant cells. To study the impact of melanoma cell-derived exosomes (MTEX) on human immune cells and melanoma progression, we isolated MTEX from total exosomes in plasma by immune capture with anti-CSPG-4 mAbs on beads. 19 proteins carried by MTEX and by non-MTEX of 12 patients with metastatic melanoma were quantified by on-bead flowcytometry. Immunoregulatory functions of these exosomes were measured in co-incubation assays with human immune cell subsets. Plasma exosomes of 6 normal donors served as controls. Melanoma-associated antigens (MAA) were present on MTEX only. MTEX carried more inhibitory ligands than non-MTEX (FasL, p<0.007; TRAIL, p<0.02), inhibited CD69 expression (p<0.002) on CD8+ T cells, suppressed T-cell proliferation (p<0.0005), and induced apoptosis of CD8+ T cells (p< 0.0005). MTEX-mediated suppression accounted for suppressive activities of total plasma exosomes. Although non-MTEX were enriched in immunostimulatory proteins (p<0.002), they induced greater suppression of NKG2D on NK cells than MTEX (p<0.001). This is the first study to show that MTEX, a subset of circulating exosomes derived from melanoma cells, are largely responsible for immuno-suppressive effects that potentially translate into systemic immune suppression and tumor promotion in melanoma patients. Citation Format: Priyanka Sharma, Brenda Diergaarde, Soldano Ferrone, John M Kirkwood, Theresa L. Whiteside. Suppression of CD8+ T-cell functions by melanoma cell-derived exosomes captured from plasma of patients with melanoma [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr B19.