Up for Mischief? IL-17/Th17 in the tumour microenvironment

Abstract

The role of IL-17 and the IL-17 producing Th17 cells in cancer has recently become the focus of extensive investigation. An expanding body of literature implicate Th17 cells and their hallmark cytokine in both pro and anti-tumourigenic processes. In this review we describe their biological activities and outline the reciprocal interactions between Th17 cells and other cells of the immune system. We also discuss the evidence regarding their dual role in the tumour microenvironment. An understanding of the processes that regulate the pro or anti-tumour activities of Th17 cell and IL-17 will allow the development of more effective means for cancer immunotherapy.

Tumor-Released Survivin Induces a Type-2 T Cell Response and Decreases Cytotoxic T Cell Function, in Vitro

“…Alteration of the immune response toward the type 2 phenotype has been demonstrated in many types of cancer, including lymphoma, breast, prostate and lung cancer, though the reason for this shift was undetermined [13][14][15][16][17]. Similar studies have been performed looking at Th17 cells in cancer patients [29,30,52,53]. Unlike the Th1/Th2 shift, which is common across patients with a variety of cancer types, the role of Th17 cells appear to Results show Mean ± SD from 3 independent experiments, n09.…”

CD200-CD200R signaling suppresses anti-tumor responses independently of CD200 expression on the tumor

“…IL-17 has a dual role in tumor development and antitumor responses (Maniati et al, 2010). IL-17 À/À mice have increased resistance for 7,12-dimethylbenzanthracene/TPA-induced skin tumors (Wang et al, 2010) whereas the same mice are less resistant to B16F10 melanoma (Kryczek et al, 2009).…”

“…Th17 cells specifically express the transcription factor RORg and are mostly known for their instrumental role in the development of autoimmune diseases (Fouser et al, 2008). The role of IL-17 and Th17 cells in the tumor microenvironment is ambiguous with reports supporting pro-and anti-tumorigenic effects of IL-17, reviewed in (Maniati et al, 2010). Th17 cells can take part in the development of anti-tumor responses by activating and/or increasing the number of tumor-penetrating effector cells (Kryczek et al, 2009;Martin-Orozco et al, 2009;Sharma et al, 2010).…”

Th17 and non-Th17 interleukin-17-expressing cells in chronic lymphocytic leukemia: delineation, distribution, and clinical relevance

“…[12][13][14][15] IL-17 has pro-and anti-tumor actions. 16,17 Functions of IL-17 relevant to cancer include angiogenesis, 18 granulopoiesis, 19 osteoclast induction, 20 and induction of cytokines such as IL-6, TGF-β, granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF), as well as matrix metalloproteinase and intercellular adhesion molecule-1 in a variety of cell types, including bone marrow stromal cells. 21,22 Because of its multitude of actions, the Th17/IL-17 axis may affect development of solid tumors (ovarian, lung, and liver cancers) [23][24][25] and hematologic cancers (myeloma, acute myeloid leukemia, and non-Hodgkin's lymphoma).…”