Rationalizing heptadecaphobia: TH17 cells and associated cytokines in cancer and metastasis

• Published in: The FEBS journal Vol. 288; no. 24; pp. 6942 - 6971
• Main Authors: Lücke, Jöran, Shiri, Ahmad Mustafa, Zhang, Tao, Kempski, Jan, Giannou, Anastasios D., Huber, Samuel
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell Publishing Ltd 01-12-2021
• Subjects: Antitumor activity; Cancer; Cytokines; Cytotoxicity; Helper cells; IL‐17A; IL‐17F; IL‐22; Immune system; Inflammation; Life expectancy; Life span; Lymphocytes; Lymphocytes T; Lymphoid cells; Metastases; Metastasis; Natural killer cells; Receptors; Retinoic acid; Tumor microenvironment; Tumors
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/febs.15711

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 (TH17) 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 γδ 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 TH17‐ and non‐TH17‐derived 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.
The cytokines IL‐17A, IL‐17F, and IL‐22 are not only produced by T helper 17 cell cells but also by T cytotoxic 17 cell, innate lymphoid cells, or γδ T cells. To date, much data have been collected describing the divergent functions of these cytokines in cancer and metastasis. Thus, this review describes the roles and regulatory mechanisms of these type 3 cytokines in different tumor entities and discusses resulting implications for future research and patient care.