Natural killer (NK) cells contribute to immunosurveillance and first-line defense in
the control of tumor growth and metastasis diffusion. NK-cell-derived extracellular
vesicles (NKEVs) are constitutively secreted and biologically active. They reflect the
protein and genetic repertoire of originating cells, and exert antitumor activity in
vitro and in vivo. Cancer can compromise NK cell functions, a status potentially
reflected by their extracellular vesicles. Hence, NKEVs could, on the one hand,
contribute to improve cancer therapy by interacting with tumor and/or immune cells
and on the other hand, sense the actual NK cell status in cancer patients. Here, we
investigated the composition of healthy donors’ NKEVs, including NK microvesicles
and exosomes, and their interaction with uncompromised cells of the immune
system. To sense the systemic NK cell status in cancer patients, we developed
an immune enzymatic test (NKExoELISA) that measures plasma NK-cell-derived
exosomes, captured as tsg101+CD56+ nanovesicles. NKEV mass spectrometry and
cytokine analysis showed the expression of NK cell markers, i.e., NKG2D and
CD94, perforin, granzymes, CD40L, and other molecules involved in cytotoxicity,
homing, cell adhesion, and immune activation, together with EV markers tsg101,
CD81, CD63, and CD9 in both NK-derived exosomes and microvesicles. Data
are available via Proteome Xchange with identifier PXD014894. Immunomodulation
studies revealed that NKEVs displayed main stimulatory functions in peripheral blood
mononuclear cells (PBMCs), inducing the expression of human leukocyte antigen DR
isotype (HLA-DR) and costimulatory molecules on monocytes and CD25 expression
on T cells, which was maintained in the presence of lipopolysaccharide (LPS) and
interleukin (IL)-10/transforming growth factor beta (TGFβ), respectively. Furthermore,
NKEVs increased the CD56+ NK cell fraction, suggesting that effects mediated by
NKEVs might be potentially exploited in support of cancer therapy. The measurement
of circulating NK exosomes in the plasma of melanoma patients and healthy donors
evidenced lower levels of tsg101+CD56+ exosomes in patients with respect to donors.
Likewise, we detected lower frequencies of NK cells in PBMCs of these patients.
These data highlight the potential of NKExoELISA to sense alterations of the NK cell
immune status