Immune Netw.  2020 Feb;20(1):e6. 10.4110/in.2020.20.e6.

IL-17-Producing Cells in Tumor Immunity: Friends or Foes?

• Kuen DS
• Kim BS
• Chung Y

• KMID: 2471046
• DOI: http://doi.org/10.4110/in.2020.20.e6

Abstract

IL-17 is produced by RAR-related orphan receptor gamma t (RORγt)-expressing cells including Th17 cells, subsets of γδT cells and innate lymphoid cells (ILCs). The biological significance of IL-17-producing cells is well-studied in contexts of inflammation, autoimmunity and host defense against infection. While most of available studies in tumor immunity mainly focused on the role of T-bet-expressing cells, including cytotoxic CD8⁺ T cells and NK cells, and their exhaustion status, the role of IL-17-producing cells remains poorly understood. While IL-17-producing T-cells were shown to be anti-tumorigenic in adoptive T-cell therapy settings, mice deficient in type 17 genes suggest a protumorigenic potential of IL-17-producing cells. This review discusses the features of IL-17-producing cells, of both lymphocytic and myeloid origins, as well as their suggested pro- and/or anti-tumorigenic functions in an organ-dependent context. Potential therapeutic approaches targeting these cells in the tumor microenvironment will also be discussed.

Keyword

Tumor microenvironment; Th17 cells; Interleukin-17; T-lymphocytes

MeSH Terms

Animals
Autoimmunity
Child
Child, Orphaned
Friends*
Humans
Inflammation
Interleukin-17
Killer Cells, Natural
Lymphocytes
Mice
T-Lymphocytes
Th17 Cells
Tumor Microenvironment
Interleukin-17

Figure

• 

  Figure 1. Type17 compartments in the tumor microenvironment. The tissue-specific niche, and the stage of cancer progression dictate the heterogeneous composition of type 17 compartment in the tumor microenvironment. Both innate and adaptive arms of the immune system are capable of producing IL-17. Studies involving both CD4+ Th17 and CD8+ Tc17 T-cells reported protumorigenic or anti-tumorigenic roles. Anti-tumorigenic Th/c17 cells co-secrete IFN-γ, and exhibit type 1–17 hybrid phenotypes that lead to enhanced dendritic cell infiltration and tumor-Ag presentation, type 1-helper function or Tc1 conversion in the case of Tc17 cells under the appropriate cytokine stimuli. However, an increasing amount of evidence illustrate the protumorigenic mechanisms (highlighted in blue) of type 17 cells within the immunosuppressive endogenous microenvironment within the growing tumor. Largely, they work by two broad mechanisms: 1) the IL-17 mediated recruitment of immunosuppressive myeloid compartment, either directly by type 17 cells or indirectly by cancer cells in a chemokine dependent manner, 2) cancer intrinsic IL-17 signaling, leading to enhanced cancer cell survival, EMT and angiogenesis promotion. EMT, epithelial–mesenchymal transition; TAM, tumor-associated macrophage.

• 

  Figure 2. Developing strategies to utilize type 17 axis for anti-cancer therapy. Currently developing strategies to transform the type 17 landscape within the tumor microenvironment for successful cancer elimination are illustrated. TAM, tumor-associated macrophage.

Reference

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