Cutting Edge: Delay and Reversal of T Cell Tolerance by Intratumoral Injection of Antigen-Loaded Dendritic Cells in an Autochthonous Tumor Model
Author(s)Higham, Eileen M.; Shen, Ching-Hung; Wittrup, Karl Dane; Chen, Jianzhu
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The tumor environment exerts a powerful suppressive influence on infiltrating tumor-reactive T cells. It induces tolerance of adoptively transferred effector T cells as they enter tumors and maintains the tolerance of persisting tumor-infiltrating T cells. In an autochthonous prostate cancer model, in which tumor-reactive CD8 T cells are trackable, we demonstrate that both depletion of endogenous dendritic cells (DCs) and intratumoral injection of Ag-loaded mature DCs delayed the tolerization of tumor-infiltrating effector CD8 T cells. Intratumoral injection of Ag-loaded DCs also reactivated tolerized CD8 T cells in the tumor tissue. The observed effects lasted as long as the injected DCs persisted. These findings are consistent with a critical role of DCs in modulating T cell reactivity in the tumor environment. They also suggest new potential strategies to extend the functionality of transferred effector T cells and to restore function to tolerized tumor-infiltrating T cells for cancer immunotherapy.
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Chemical Engineering
Journal of Immunology
The American Association of Immunologists
Higham, E. M. et al. “Cutting Edge: Delay and Reversal of T Cell Tolerance by Intratumoral Injection of Antigen-Loaded Dendritic Cells in an Autochthonous Tumor Model.” The Journal of Immunology 184.11 (2010): 5954–5958.
Author's final manuscript