NKT cells in the antitumor response: the β version?

J Clin Invest. 2024 Feb 15;134(4):e177663. doi: 10.1172/JCI177663.

Abstract

NKT cells recognize glycolipids presented by CD1d-expressing antigen-presenting cells (APCs) and include type I NKT cells with antitumor function and type II NKT cells, which have been reported to suppress the antitumor response. Some type II NKT cells recognize sulfatide, a glycosphingolipid with a sulfate modification of the sugar. Type I NKT cells recognize different glycosphingolipids. In this issue of the JCI, Nishio and colleagues showed that APCs could process sulfatide antigens, analogous to protein processing for peptide-reactive T cells. Antigen processing in lysosomes removed sulfate to generate a glycosphingolipid that stimulated type I NKT cells and thereby turned an antigen with no antitumor activity into one that not only stimulated type I NKT cells but also stimulated antitumor responses. These findings may extend to the development of glycolipid antigens that could stimulate anticancer responses via antigen processing by APCs.

MeSH terms

  • Antigens, CD1d
  • Glycolipids / metabolism
  • Glycosphingolipids / metabolism
  • Natural Killer T-Cells*
  • Sulfates / metabolism
  • Sulfoglycosphingolipids / metabolism

Substances

  • Sulfoglycosphingolipids
  • Antigens, CD1d
  • Glycolipids
  • Glycosphingolipids
  • Sulfates