Developing understanding of the roles of CD1d-restricted T cell subsets in cancer: Reversing tumor-induced defects

作者：Exley Mark A^*; Lynch Lydia; Varghese Bindu; Nowak Michael; Alatrakchi Nadia; Balk Steven P

来源：Clinical Immunology, 2011, 140(2): 184-195.

DOI：10.1016/j.clim.2011.04.017

• Cytokines
• Tumor immunity
• CD1
• CD1d-reactive T cells
• iNKT
• NKT

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 Cold. 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.

• 出版日期2011-8