title: Developing understanding of the roles of CD1d-restricted T cell subsets in cancer: reversing tumor-induced defects.
abstract: Invariant natural killer T-cells ('iNKT') are the best-known CD1d-restricted T-cells, with recently-defined roles in controlling adaptive immunity. CD1d-restricted T-cells can rapidly produce large amounts of Th1 and/or Th2//Treg/Th17-type cytokines, thereby regulating immunity. iNKT can stimulate potent anti-tumor immune responses via production of Th1 cytokines, direct cytotoxicity, and activation of effectors. However, Th2//Treg-type iNKT can inhibit anti-tumor activity. Furthermore, iNKT are decreased and/or reversibly functionally impaired in many advanced cancers. In some cases, CD1d-restricted T-cell cancer defects can be traced to CD1d(+) tumor interactions, since hematopoietic, prostate, and some other tumors can express CD1d. Ligand and IL-12 can reverse iNKT defects and therapeutic opportunities exist in correcting such defects alone and in combination. Early stage clinical trials have shown potential for reconstitution of iNKT IFN-gamma responses and evidence of activity in a subset of patients, with rational new approaches to capitalize on this progress ongoing, as will be discussed here.
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. mexley@bidmc.harvard.edu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Exley
authors.forename: Lydia
authors.initials: L
authors.lastname: Lynch
authors.forename: Bindu
authors.initials: B
authors.lastname: Varghese
authors.forename: Michael
authors.initials: M
authors.lastname: Nowak
authors.forename: Nadia
authors.initials: N
authors.lastname: Alatrakchi
authors.forename: Steven P
authors.initials: SP
authors.lastname: Balk
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D055610:Antigens, CD1d / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005699:Galactosylceramides / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D018448:Models, Immunological; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D055610:Antigens, CD1d; D016207:Cytokines; D005699:Galactosylceramides