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Current Molecular Medicine
ISSN (Print): 1566-5240
ISSN (Online): 1875-5666
VOLUME: 9
ISSUE: 6
DOI: 10.2174/156652409788970706      Price:  $58









The Contrasting Roles of NKT Cells in Tumor Immunity

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Author(s): Jay A. Berzofsky and Masaki Terabe
Pages 667-672 (6)
Abstract:
NKT cells are true T cells that serve as a bridge between the innate and adaptive immune system, acting as first responders. They recognize lipid antigens rather than peptides, and respond to these when presented by a non-classical class I MHC molecule, CD1d. NKT cells can play a pathogenic role in asthma or a protective role against several autoimmune diseases, in part based on their cytokine profile. In cancer, they can play opposite roles, contributing to anti-tumor immunity or suppressing it. The protective NKT cells were found to be primarily type I NKT cells defined by use of a semi-invariant T cell receptor involving Vα14Jα18 in mice and Vα24Jα18 in humans and responding to α-galactosylceramide, and the most protective were among the minority that are CD4-. The suppressive NKT cells were found to be CD4+ and to be primarily type II NKT cells, that have diverse T-cell receptors and respond to other lipids. Further, the type I and type II NKT cells were found to counter-regulate each other, forming a new immunoregulatory axis. This axis may have broad implications beyond cancer, as NKT cells play a role in steering other adaptive immune responses. The balance along this axis could affect immunity to tumors and infectious diseases and responses to vaccines.
Keywords:
NKT cells, tumor immunity, immunosurveillance, immunoregulation, α-galactosylceramide, cancer, IL-13, TGF-β
Affiliation:
Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1578, USA.