4.6 Article

Oral cancer cell-derived exosomes modulate natural killer cell activity by regulating the receptors on these cells

Journal

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
Volume 46, Issue 6, Pages 2115-2125

Publisher

SPANDIDOS PUBL LTD
DOI: 10.3892/ijmm.2020.4736

Keywords

oral cancer cells; exosomes; transforming growth factor β 1; natural killer cells

Funding

  1. National Key Research and Development Program of China [2016YFC0902700]
  2. National Natural Science Foundation of China [81874126, 91229103, 81672 745]
  3. Shanghai Science and Technology Commission [18DZ2291500]

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Oral cancer (OC) is the most common type of head and neck malignant tumor. Tumor-derived exosomes induce a complex extracellular environment that affects tumor immunity. In the present study, exosomes were isolated from OC cell lines (WSU-HN4 and SCC-9) by ultrafiltration and the protein content of these oral cancer-derived exosomes (OCEXs) was analyzed by mass spectrometry, which revealed the enrichment of transforming growth factor (TGF)-beta 1. Natural killer (NK) cells were examined by flow cytometry following co-culture with OCEXs. The expression of killer cell lectin like receptor K1 (KLRK1; also known as NKG2D, as used herein) and natural cytotoxicity triggering receptor 3 (NCR3; also known as NKp30, as used herein) in NK cells was found to be significantly upregulated following co-culture with the OCEXs for 1 day, whereas this expression decreased at 7 days. Killer cell lectin like receptor C1 (KLRC1; also known as NKG2A; as used herein) expression exhibited an opposite trend at 1 day. In addition, NK cell cytotoxicity against the OC cells was enhanced at 1 day, but was attenuated at 7 days. TGF-beta 1 inhibited the function of NK cells at 7 days, whereas it had no obvious effects at 1 and 3 days. On the whole, the findings of the present study reveal changes in NK cell function and provide new insight into NK cell dysfunction.

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