Abstract:
: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.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Dokouhaki P,Schuh NW,Joe B,Allen CA,Der SD,Tsao MS,Zhang Ldoi
10.1002/eji.201243150subject
Has Abstractpub_date
2013-12-01 00:00:00pages
3175-82issue
12eissn
0014-2980issn
1521-4141journal_volume
43pub_type
杂志文章abstract::The T cell-dependent differentiation and function of B lymphocytes are tightly regulated by TNF ligands (L) and receptors interactions, such as CD40/CD40L, CD27/CD70 and CD134/CD314L. The LIGHT/HVEM system [homologous to lymphotoxin, inducible expression, competing for GpD of herpes virus, that binds to the herpes vir...
journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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doi:10.1002/eji.1830270605
更新日期:1997-06-01 00:00:00
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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