The contribution of NKT cells, NK cells, and other gamma-chain-dependent non-T non-B cells to IL-12-mediated rejection of tumors.

Abstract

IL-12 is a potent cytokine that impairs the growth of several tumors in vivo in natural as well as in therapeutic conditions. Although IL-12 can enhance a number of immunological antitumor mechanisms, including those mediated by NK cells and CTL, recent reports have suggested that the mouse CD1d-restricted V alpha 14-J alpha 18 NKT cell was the essential cell type recruited in most, if not all tumor rejection models, including the B16 melanoma. In this study, we have examined and compared the role of NKT cells, T cells, NK cells, and other non-T non-B cells in the rejection of B16 melanoma cells after exogenous administration of IL-12. Surprisingly, our results failed to confirm a necessary role for NKT cells in this model. Instead, we found that NK cells mediated the rejection of liver metastases, whereas other gamma c-dependent non-T non-B cells, possibly lymphoid dendritic cells, were required for rejection of skin tumors. These findings challenge the view that NKT cells are systematically required for IL-12-mediated rejection of tumors, and instead reveal that a variety of effector pathways can be recruited depending on the tumor microenvironment.

• Authors: Se-Ho Park, Tim Kyin, Albert Bendelac, Claude Carnaud
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 170 Issue 3 Pg. 1197-201 (Feb 01 2003) ISSN: 0022-1767 [Print] United States
• PMID: 12538676 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Il2rg protein, mouse
• Interleukin Receptor Common gamma Subunit
• Receptors, Interleukin-7
• Interleukin-12

Topics

• Animals
• Antineoplastic Agents (administration & dosage, therapeutic use)
• B-Lymphocyte Subsets (immunology)
• Drug Administration Schedule
• Graft Rejection (genetics, immunology)
• Injections, Intralesional
• Injections, Intraperitoneal
• Injections, Intravenous
• Injections, Subcutaneous
• Interleukin Receptor Common gamma Subunit
• Interleukin-12 (administration & dosage, physiology, therapeutic use)
• Killer Cells, Natural (immunology)
• Lymphocyte Activation (immunology)
• Lymphocyte Depletion
• Melanoma, Experimental (genetics, immunology, prevention & control)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Receptors, Interleukin-7 (physiology)
• T-Lymphocyte Subsets (immunology)
• Tumor Cells, Cultured