Cutting Edge: Delay and Reversal of T Cell Tolerance by Intratumoral Injection of Antigen-Loaded Dendritic Cells in an Autochthonous Tumor Model
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Author(s)
Higham, Eileen M.
Wittrup, Karl Dane
Chen, Jianzhu
Shen, Chase
Date Issued
April 2010
Journal
Journal of Immunology
Publisher
The American Association of Immunologists
Citation
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.
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Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.4049/jimmunol.1000265
