Cancer immunotherapy using NKG2D and DNAM-1 systems.
Although tumor antigen-specific immunotherapy, such as dendritic cell vaccine, has recently emerged as a promising clinical approach, one limitation of tumor antigen- and T-cell receptor (TcR)-specific immunotherapy is antigen-specific inhibition by antigen-specific regulatory T-cell and myeloid suppressor cells. Therefore, immunotherapy using a TcR-independent mechanism may be an alternative immunotherapeutic strategy. NKG2D (natural killer, group 2, member D) and DNAX accessory molecule-1 (DNAM-1) are both activated receptors that are strongly expressed on T-cells, γδT-cells, and NK cells. Therefore, the expression of ligands for NKG2D and DNAM-1 on tumor cells plays an important role in tumor opsonization by immune effector cell targeting. Various modulatory methods for up-regulating NKG2D and DNAM-1-ligands have been reported, and included chemotherapeutic agents and hyperthermia. Although there are many obstacles to the utilization of NKG2D and DNAM-1 for cancer therapy, combined treatments using immune cell therapy and chemotherapy that take advantage of NKG2D and DNAM-1 may be an ideal approach.
Fukuoka General Cancer Clinic, 3-1-1 Sumiyoshi, Hakata-ku, Fukuoka 812-0018, Japan. tmorisaki@cancer-clinic.jp
Takashi
T
Morisaki
Hideya
H
Onishi
Mitsuo
M
Katano
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007694:Killer Cells, Natural / Q000276:immunology; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology* / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D000098862:T Lineage-Specific Activation Antigen 1
D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K