title: Isopentenyl pyrophosphate-activated CD56+ {gamma}{delta} T lymphocytes display potent antitumor activity toward human squamous cell carcinoma.
abstract: 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.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, MD 21201, USA.
authors.forename: Alan A Z
authors.initials: AA
authors.lastname: Alexander
authors.forename: Amudhan
authors.initials: A
authors.lastname: Maniar
authors.forename: Jean-Saville
authors.initials: JS
authors.lastname: Cummings
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Hebbeler
authors.forename: Dan H
authors.initials: DH
authors.lastname: Schulze
authors.forename: Brian R
authors.initials: BR
authors.lastname: Gastman
authors.forename: C David
authors.initials: CD
authors.lastname: Pauza
authors.forename: Scott E
authors.initials: SE
authors.lastname: Strome
authors.forename: Andrei I
authors.initials: AI
authors.lastname: Chapoval
mesh_terms: 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*
chemical_list: 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