Key Points
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T helper 17 (TH17) cells are found in human and mouse tumours. However, the numbers of TH17 cells are limited and are lower than that of other T cell subsets, such as regulatory T (TReg) cells, in the same tumour microenvironment.
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TH17 cells exhibit polyfunctional features and express several effector cytokines, including interleukin-2 (IL-2), IL-17, granulocyte–macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFNγ) and tumour necrosis factor (TNF) in the human tumour microenvironment.
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TH17 cells and IL-17-producing CD8+ T cells induce potent tumour eradication in mice.
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Tumour-infiltrating TReg cells suppress TH17 cell expansion in tumours, partly through the adenosinergic pathway.
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The antitumour activity of TH17 cells may be due to their ability to recruit effector T cells, natural killer cells and dendritic cells into the tumour environment and to tumour-draining lymph nodes.
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The mechanistic and functional relationship between TH17 cells, TH17 cell-associated cytokines (IL-17 and IL-23) and tumour immunopathology is likely to be highly context dependent.
Abstract
T helper 17 (TH17) cells have well-described roles in autoimmune disease. Recent evidence suggests that this effector T cell subset is also involved in tumour immunology and may be a _target for cancer therapy. In this Review, we summarize recent findings regarding the nature and relevance of TH17 cells in mouse models of cancer and human disease. We describe the interplay between TH17 cells and other immune cells in the tumour microenvironment, and we assess both the potential antitumorigenic and pro-tumorigenic activities of TH17 cells and their associated cytokines. Understanding the nature of TH17 cell responses in the tumour microenvironment will be important for the design of more efficacious cancer immunotherapies.
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Change history
25 July 2011
In the original version of this article, in the section under the subheading “IL-17 and TH17 cells” on page 252, the sentence that began “Furthermore, although IL-17 deficiency leads to increased numbers of IFNγ-producing NK cells in the tumour-draining lymph nodes” was incorrect. This sentence should instead begin “Furthermore, although IL-17 deficiency leads to decreased numbers of IFNγ-producing NK cells in the tumour-draining lymph nodes”. The authors apologize for this error.
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Acknowledgements
We thank our former and current trainees and collaborators for their intellectual input and hard work. The work described in this Review was supported by the extramural (W.Z.) and intramural (N.P.R.) funds from the United States National Cancer Institute.
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Glossary
- Regulatory T (TReg) cells
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A specialized subset of CD4+ T cells that can suppress inflammation and the responses of other T cells. These cells provide a crucial mechanism for the maintenance of peripheral self tolerance. A subset of these cells is characterized by expression of CD25 and the transcription factor FOXP3.
- Granzyme B
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A secreted serine protease that enters _target cells through perforin pores, it then cleaves and activates intracellular caspases, leading to _target-cell apoptosis.
- Plasmacytoid dendritic cells
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A subset of dendritic cells that is described as plasmacytoid because their microscopic appearance resembles plasmablasts. In humans, these cells can be derived from lineage-negative stem cells in peripheral blood and are the main producers of type I IFN in response to virus infections.
- Indoleamine 2,3-dioxygenase
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(IDO). An intracellular haeme-containing enzyme that catalyses the oxidative catabolism of tryptophan. Insufficient availability of tryptophan can lead to T cell apoptosis and anergy.
- Cytotoxic T lymphocyte antigen 4
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(CTLA4). A T cell surface protein that, following its ligation by CD80 or CD86 on antigen-presenting cells, delivers a negative signal to activated T cells. This induces cell cycle arrest and inhibits cytokine production. CTLA4 is constitutively expressed by, and functionally associated with, regulatory T cells.
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Zou, W., Restifo, N. TH17 cells in tumour immunity and immunotherapy. Nat Rev Immunol 10, 248–256 (2010). https://doi.org/10.1038/nri2742
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DOI: https://doi.org/10.1038/nri2742
