Rationalizing heptadecaphobia: T_H17 cells and associated cytokines in cancer and metastasis

Abstract

Cancer is one of the leading causes of death worldwide. When cancer patients are diagnosed with metastasis, meaning that the primary tumor has spread to at least one different site, their life expectancy decreases dramatically. In the past decade, the immune system´s role in fighting cancer and metastasis has been studied extensively. Importantly, immune cells and inflammatory reactions generate potent antitumor responses but also contribute to tumor development. However, the molecular and cellular mechanisms underlying this dichotomic interaction between the immune system and cancer are still poorly understood. Recently, a spotlight has been cast on the distinct subsets of immune cells and their derived cytokines since evidence has implicated their crucial impact on cancer development. T helper 17 cell (T H 17) cells, which express the master transcriptional factor Retinoic acid-receptor-related orphan receptor gamma t, are among these critical cell subsets and are defined by their production of type 3 cytokines, such as IL-17A, IL-17F, and IL-22. Depending on the tumor microenvironment, these cytokines can also be produced by other immune cell sources, such as T cytotoxic 17 cell, innate lymphoid cells, NKT cells, or cd T cells. To date, a lot of data have been collected describing the divergent functions of IL-17A, IL-17F, and IL-22 in malignancies. In this comprehensive review, we discuss the role of these T H 17-and non-T H 17derived type 3 cytokines in different tumor entities. Furthermore, we will provide a structured insight into the strict regulation and subsequent downstream mechanisms of these cytokines in cancer and metastasis.

Inhibitors of the Actin-Bundling Protein Fascin-1 Developed for Tumor Therapy Attenuate the T-Cell Stimulatory Properties of Dendritic Cells

“…It remains possible that each Fscn1 inhibitor may evoke distinct off-target effects, as evidenced by the inhibitory versus stimulatory effect of NP-G2-044 and BDP-13176 on F-actin levels, respectively, as well as the coactivating potential of NP-G2-044 in CD8 + T cells. Furthermore, we also noted that treatment of DC/T-cell cocultures with BDP-13176 but not NP-G2-044 at low to intermediate concentrations favored production Th2- (IL-13) and Th9- (IL-9) [ 46 ] associated cytokines, whereas NP-G2-044 at the lowest concentration upregulated Th17-associated IL-17 [ 47 ] production.…”

CD4+ T cell-derived IL-22 enhances liver metastasis by promoting angiogenesis

“…Notably, several immune cells can produce IL-22, for example, Th22, Th17, ILC3, and NKT cells. 19 , 34 , 35 We previously showed that NKT cells and T cells are the key sources during the early step of metastasis, namely extravasation, in liver and lung metastasis, respectively. 19 Interestingly, in established lung metastasis, Th22 cells were identified as the key source of IL-22 in the lung.…”

Th17 cells target the metabolic miR-142-5p-SDHC/SDHD axis promoting invasiveness and progression of cervical cancers

“…Th17 cells have a controversial role in different cancers. They mediate antitumor effects by recruiting immune cells into tumors or stimulating effector CD8 + T cells (26) as well as tumor-promoting responses driving proliferation, invasion, metastasis, and angiogenesis (27,28). Although the presence of Th17 cells in situ was linked with cervical cancer progression (6,10), and IL-17A was found to upregulate MMP-2 and MMP-9 expression favoring migration of cervical cancer cell lines (27), Th17-induced mechanisms underlying cervical cancer metastases are not reported so far.…”