Mechanisms of Invariant Natural Killer T Cell-Mediated Immunoregulation in Cancer
Abstract
Invariant natural killer (iNKT) cells are a unique population of immune cells that rapidly secrete a variety of cytokines upon activation and have been generally attributed potent anti-tumor functions. However, our studies using the murine 4T1 breast cancer model indicate a regulatory/suppressive function that markedly inhibits effector response generated by combined radiotherapy and immunotherapy to either CTLA-4 or 4-1BB (CD137), resulting in dramatic improvement in survival in NKT-/- mice. Our data also indicate that regulatory iNKT cells may act at the level of antigen presentation since NKT-/- mice were found to have significantly more dendritic cells of a highly mature phenotype than wild-type tumor mice. Regulatory function could not be rescued by in vivo administration of a strong Th1-inducing NKT agonist -galactosyleramide; we hypothesize that blocking antibodies to CD1d (clone 20H2) will relieve this immunosuppression. We have spent considerable time in ensuring that the blocking antibody will not have any secondary effects that include depletion or stimulation of CD1d-expressing DCs. Studies are now underway to test whether blocking this interaction will abrogate the suppressive effect of iNKT cells on therapy-induced anti-tumor immune response.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2012
- Accession Number
- ADA589025
Entities
People
- Karsten A. Pilones
Organizations
- New York University