Potential of human gammadelta T lymphocytes for immunotherapy of cancer.
T lymphocytes are classified into 2 subsets based on their T-cell receptor (TCR) expression. The vast majority of T cells expresses an alphabeta TCR heterodimer. These alphabeta T cells recognize antigenic peptides presented by MHC class I (for CD8(+) T cells) or MHC class II molecules (for CD4(+) T cells). Concepts of cancer immunotherapy are mostly concerned with activation of these MHC-restricted alphabeta T cells. Until recently, a numerically small subset of T cells, which expresses an alternative TCR composed of a CD3-associated gammadelta heterodimer, has received far less attention as a potential agent in cancer therapy. These gammadelta T cells share with alphabeta T cells certain effector functions such as cytokine production and potent cytotoxic activity but recognize different sets of antigens, usually in a non-MHC-restricted fashion. Different subsets of human gammadelta T cells recognize stress-inducible MHC class I-related molecules frequently expressed on epithelial tumor cells or phosphorylated metabolites which can be generated by tumor cells. In line with this, many tumor cells are highly susceptible to gammadelta T-cell mediated lysis. In our article, we summarize the available evidence for a contribution of human gammadelta T cells in tumor defense and discuss potential strategies for the immunotherapy of tumors based on the endogenous activation and/or adoptive transfer of tumor-reactive gammadelta T lymphocytes.
Kabelitz
Dieter
D
Institute of Immunology, UKS-H Campus Kiel, Kiel, Germany. kabelitz@immunologie.uni-kiel.de
Wesch
Daniela
D
Pitters
Elke
E
Zöller
Margot
M
D000951:Antigens, Neoplasm / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008024:Ligands; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000951:Antigens, Neoplasm; D017252:CD3 Complex; D008024:Ligands