title: Cross-regulation between type I and type II NKT cells in regulating tumor immunity: a new immunoregulatory axis.
abstract: Negative immunoregulation is a major barrier to successful cancer immunotherapy. The NKT cell is known to be one such regulator. In this study we explored the roles of and interaction between the classical type I NKT cell and the poorly understood type II NKT cell in the regulation of tumor immunity. Selective stimulation of type II NKT cells suppressed immunosurveillance, whereas stimulation of type I NKT cells protected against tumor growth even when responses were relatively skewed toward Th2 cytokines. When both were stimulated simultaneously, type II NKT cells appeared to suppress the activation in vitro and protective effect in vivo of type I NKT cells. In the absence of type I, suppression by type II NKT cells increased, suggesting that type I cells reduce the suppressive effect of type II NKT cells. Thus, in tumor immunity type I and type II NKT cells have opposite and counteractive roles and define a new immunoregulatory axis. Alteration of the balance between the protective type I and the suppressive type II NKT cell may be exploited for therapeutic intervention in cancer.
authors.affiliation: National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Ambrosino
authors.forename: Masaki
authors.initials: M
authors.lastname: Terabe
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Halder
authors.forename: Judy
authors.initials: J
authors.lastname: Peng
authors.forename: Shun
authors.initials: S
authors.lastname: Takaku
authors.forename: Sachiko
authors.initials: S
authors.lastname: Miyake
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamura
authors.forename: Vipin
authors.initials: V
authors.lastname: Kumar
authors.forename: Jay A
authors.initials: JA
authors.lastname: Berzofsky
mesh_terms: D000818:Animals; D018949:Antigens, CD1 / Q000276:immunology; D055610:Antigens, CD1d; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology* / Q000517:prevention & control; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology* / Q000517:prevention & control; D007165:Immunosuppression Therapy; D007694:Killer Cells, Natural / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000276:immunology* / Q000378:metabolism
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d