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

Mark A. Exley, Lydia Lynch, Bindu Varghese, Michael Nowak, Nadia Alatrakchi, Steven P. Balk

Research output: Contribution to journalReview articlepeer-review

41 Scopus citations

Abstract

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 CD1d. 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.

Original languageEnglish (US)
Pages (from-to)184-195
Number of pages12
JournalClinical Immunology
Volume140
Issue number2
DOIs
StatePublished - Aug 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Keywords

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

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