NKG2D regulates production of soluble TRAIL by ex vivo expanded human γδ T cells

Soluble TRAIL (sTRAIL) can be produced by myeloid‐derived cells to kill cancer cells. Whether this mechanism is used by T cells, and if so, how sTRAIL production is regulated, remains unclear. Our previous studies showed that ex vivo expanded human γδ T cells express TRAIL and NK receptor group 2 (R...

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Veröffentlicht in:European journal of immunology 2013-12, Vol.43 (12), p.3175-3182
Hauptverfasser: Dokouhaki, Pouneh, Schuh, Nicholas W., Joe, Betty, Allen, Christopher A. D., Der, Sandy D., Tsao, Ming‐Sound, Zhang, Li
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Sprache:eng
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Zusammenfassung:Soluble TRAIL (sTRAIL) can be produced by myeloid‐derived cells to kill cancer cells. Whether this mechanism is used by T cells, and if so, how sTRAIL production is regulated, remains unclear. Our previous studies showed that ex vivo expanded human γδ T cells express TRAIL and NK receptor group 2 (R2), member D (NKG2D), and possess potent anticancer activities both in vitro and in vivo. Here, we investigated in greater detail the mechanisms by which γδ T cells utilize TRAIL and NKG2D to kill lung cancer cells. We demonstrate that human lung cancer cells express TRAIL R2 and NKG2D ligands. Blocking TRAIL or NKG2D during γδ T‐cell‐lung cancer cell co‐cultures significantly reduced γδ T‐cell‐mediated cytotoxicity. Cross‐linking NKG2D with anti‐NKG2D antibody to mimic ligand binding promoted γδ T cells to produce sTRAIL, which induced apoptosis in lung cancer cells through TRAIL R2. Either neutralizing sTRAIL or blocking lung cancer cell TRAIL R2 significantly reduced γδ T‐cell‐mediated cytotoxicity to lung cancer cells. This study demonstrates that γδ T cells can mediate anticancer immunity via NKG2D‐regulated production of sTRAIL.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.201243150