Isopentenyl pyrophosphate-activated CD56+ {gamma}{delta} T lymphocytes display potent antitumor activity toward human squamous cell carcinoma.
OBJECTIVE
The expression of CD56, a natural killer cell-associated molecule, on alphabeta T lymphocytes correlates with their increased antitumor effector function. CD56 is also expressed on a subset of gammadelta T cells. However, antitumor effector functions of CD56(+) gammadelta T cells are poorly characterized.


METHODS
To investigate the potential effector role of CD56(+) gammadelta T cells in tumor killing, we used isopentenyl pyrophosphate and interleukin-2-expanded gammadelta T cells from peripheral blood mononuclear cells of healthy donors.


RESULTS
Thirty to 70% of expanded gammadelta T cells express CD56 on their surface. Interestingly, although both CD56(+) and CD56(-) gammadelta T cells express comparable levels of receptors involved in the regulation of gammadelta T-cell cytotoxicity (e.g., NKG2D and CD94), only CD56(+) gammadelta 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(+) gammadelta 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-gammadelta T-cell receptor + anti-NKG2D monoclonal antibody, suggesting that the lytic activity of CD56(+) gammadelta T cells involves the perforin-granzyme pathway and is mainly gammadelta T-cell receptor/NKG2D dependent. Importantly, CD56-expressing gammadelta T lymphocytes are resistant to Fas ligand and chemically induced apoptosis.


CONCLUSIONS
Our data indicate that CD56(+) gammadelta T cells 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.
Alexander
Alan A Z
AA
Department of Otorhinolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, MD 21201, USA.
Maniar
Amudhan
A
Cummings
Jean-Saville
JS
Hebbeler
Andrew M
AM
Schulze
Dan H
DH
Gastman
Brian R
BR
Pauza
C David
CD
Strome
Scott E
SE
Chapoval
Andrei I
AI
D000970:Antineoplastic Agents / Q000494:pharmacology*; D019002:CD56 Antigen / Q000096:biosynthesis*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D053804:Granzymes / Q000737:chemistry; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D045782:Hemiterpenes / Q000494:pharmacology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007376:Interleukin-2 / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D054353:Perforin / Q000737:chemistry; D010641:Phenotype; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D000970:Antineoplastic Agents; D019002:CD56 Antigen; D045782:Hemiterpenes; D007376:Interleukin-2; D009943:Organophosphorus Compounds; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054353:Perforin; C004809:isopentenyl pyrophosphate; D053804:Granzymes