Harnessing human CD1d restricted T cells for tumor immunity: progress and challenges
Madhav V. Dhodapkar1,2
1
Hematology Section, Yale University School of Medicine, New Haven, CT 06510, USA, 2Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, New York, NY 10065, USA
TABLE OF CONTENTS
- 1. Abstract
- 2. Introduction
- 3. Diversity of CD1d restricted natural killer T cells
- 4. Tissue distribution and subsets of CD1d restricted T cells in humans and mice
- 5. Anti-tumor properties of NKT cells in mice
- 6. Enhancement of tumor growth by type II NKT cells
- 7. Studies of NKT cells in human cancer
- 8. Manipulating human NKT cells in vivo
- 8.1. Soluble a-GalCer therapy
- 8.2. a-GalCer loaded dendritic cells
- 9. Improving NKT targeting in the clinic
- 9.1. Patient Selection
- 9.2. Alternate ligands
- 9.3. Combination Therapies
- 9.4. Harnessing adjuvant properties of NKT cells
- 10. Challenges for targeting NKT cells in the clinic
- 10.1. Humans versus mice
- 10.2. Type I versus II NKT cells
- 10.3. Role of tissue and tumor microenvironments
- 11. Summary
- 12. Acknowledgments
- 13. References
1. ABSTRACT
Glycolipid reactive CD1d restricted natural killer T (NKT) cells represent a distinct population of T cells implicated in the regulation of immune responses in a broad range of diseases including cancer. Several studies have demonstrated the capacity of NKT cells bearing an invariant T cell receptor (iNKT cells) to recruit both innate and adaptive anti-tumor immunity and mediate tumor rejection in mice. Early phase clinical studies in humans have demonstrated the capacity of dendritic cells (DCs) to mediate expansion of NKT cells in vivo. However several challenges need to be overcome in order to effectively harness the properties of these cells in the clinic.
