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Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

The Contrasting Roles of NKT Cells in Tumor Immunity

Author(s): Jay A. Berzofsky and Masaki Terabe

Volume 9, Issue 6, 2009

Page: [667 - 672] Pages: 6

DOI: 10.2174/156652409788970706

Price: $65

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


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