TY - JOUR
T1 - Isopentenyl pyrophosphate-activated CD56+ γδ T lymphocytes display potent antitumor activity toward human squamous cell carcinoma
AU - Alexander, Alan A.Z.
AU - Maniar, Amudhan
AU - Cummings, Jean Saville
AU - Hebbeler, Andrew M.
AU - Schulze, Dan H.
AU - Gastman, Brian R.
AU - Pauza, C. David
AU - Strome, Scott E.
AU - Chapoval, Andrei I.
PY - 2008/7/1
Y1 - 2008/7/1
N2 - Purpose: The expression of CD56, a natural killer cell - associated molecule, on αβ T lymphocytes correlates with their increased antitumor effector function. CD56 is also expressed on a subset of γδ T cells. However, antitumor effector functions of CD56 + γδ Tcells are poorly characterized. Experimental Design: To investigate the potential effector role of CD56+ γδ Tcells in tumor killing, we used isopentenyl pyrophosphate and interleukin-2- expanded γδ T cells from peripheral blood mononuclear cells of healthy donors. Results: Thirty to 70% of expanded γδ Tcells express CD56 on their surface. Interestingly, although both CD56 + and CD56- γδ Tcells express comparable levels of receptors involved in the regulation of γδ T-cell cytotoxicity (e.g., NKG2D and CD94), only CD56+ γδ T lymphocytes are capable of killing squamous cell carcinoma and other solid tumor cell lines. This effect is likely mediated by the enhanced release of cytolytic granules because CD56+ γδ T lymphocytes expressed higher levels of CD107a compared with CD56- controls following exposure to tumor cell lines. Lysis of tumor cell lines is blocked by concanamycin A and a combination of anti-γδ T-cell receptor + anti-NKG2D monoclonal antibody, suggesting that the lytic activity of CD56+ γδ Tcells involves the perforin-granzyme pathway and is mainly γδT-cell receptor/NKG2D dependent. Importantly, CD56-expressing γδT lymphocytes are resistant to Fas ligand and chemically induced apoptosis. Conclusions: Our data indicate that CD56+ γδ Tcells are potent antitumor effectors capable of killing squamous cell carcinoma and may play an important therapeutic role in patients with head and neck cancer and other malignancies.
AB - Purpose: The expression of CD56, a natural killer cell - associated molecule, on αβ T lymphocytes correlates with their increased antitumor effector function. CD56 is also expressed on a subset of γδ T cells. However, antitumor effector functions of CD56 + γδ Tcells are poorly characterized. Experimental Design: To investigate the potential effector role of CD56+ γδ Tcells in tumor killing, we used isopentenyl pyrophosphate and interleukin-2- expanded γδ T cells from peripheral blood mononuclear cells of healthy donors. Results: Thirty to 70% of expanded γδ Tcells express CD56 on their surface. Interestingly, although both CD56 + and CD56- γδ Tcells express comparable levels of receptors involved in the regulation of γδ T-cell cytotoxicity (e.g., NKG2D and CD94), only CD56+ γδ T lymphocytes are capable of killing squamous cell carcinoma and other solid tumor cell lines. This effect is likely mediated by the enhanced release of cytolytic granules because CD56+ γδ T lymphocytes expressed higher levels of CD107a compared with CD56- controls following exposure to tumor cell lines. Lysis of tumor cell lines is blocked by concanamycin A and a combination of anti-γδ T-cell receptor + anti-NKG2D monoclonal antibody, suggesting that the lytic activity of CD56+ γδ Tcells involves the perforin-granzyme pathway and is mainly γδT-cell receptor/NKG2D dependent. Importantly, CD56-expressing γδT lymphocytes are resistant to Fas ligand and chemically induced apoptosis. Conclusions: Our data indicate that CD56+ γδ Tcells are potent antitumor effectors capable of killing squamous cell carcinoma and may play an important therapeutic role in patients with head and neck cancer and other malignancies.
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U2 - 10.1158/1078-0432.CCR-07-4912
DO - 10.1158/1078-0432.CCR-07-4912
M3 - Article
C2 - 18594005
AN - SCOPUS:48249107111
SN - 1078-0432
VL - 14
SP - 4232
EP - 4240
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 13
ER -