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 implicated in a autoimmune diseases, infection as well as cancer. In cancer, iNKT cells have generally been attributed potent anti-tumor functions but our studies using the murine 4T1 mammary carcinoma indicate a regulatory/ suppressive function that markedly affects response to treatment with radioimmunotherapy. We proposed to test the novel hypothesis that iNKT cells can be conditioned by the breast tumor environment to switch to an immunoregulatory phenotype. Specifically, three non-mutually exclusive hypothesis will be tested 1) that a lipid antigen derived from 4T1 tumor cells can be presented by dendritic cells and induce the preferential secretion of immunosuppressive cytokines; 2)that iNKT cells inhibit effector T cell priming by killing dendritic cells and 3) that immunoregulatory iNKT cells can promote the generation and maintenance of regulatory T-cells. Thus far, we have made significant progress in demonstrating that lipid antigen/s derived from 4T1 tumors can differentially modulate the maturational markers in dendritic cells. Mechanistic studies addressing effects on cross-priming are being planned for the second year.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2011
- Accession Number
- ADA549275
Entities
People
- Karsten Pilones
Organizations
- New York University