The role of Th17 cells in chronic lymphocytic leukemia: friend or foe?

T helper 17 (Th17) cells have a prominent role in autoimmune diseases. In contrast, the nature of these cells in cancer is controversial, with either pro or anti-tumorigenic activities depending on various cancer settings. Chronic lymphocytic leukemia (CLL), a B-cell malignancy, is characterized by an imbalance in T-cell immune responses contributing to disease progression and increased mortality. Many clinical reports indicate an increase in Th17 cells and/or IL-17 serum cytokine levels in CLL patients compared to healthy individuals which correlates with various prognostic markers and significant changes in the tumor microenvironment. The exact mechanisms by which Th17 might contribute to CLL progression is still less investigated. In this review, we provide an updated presentation of the clinical information related to the significance of Th17 cells in CLL, and their interaction with the complex leukemic microenvironment including various mediators, immune and non-immune cells. Herein, we also address the available data regarding the effects of CLL targeted therapies on Th17 cells, and the potential of using these cells in adoptive cell therapies. Having a sound understanding of the role played by Th17 in CLL is crucial for designing novel therapies that can achieve immune homeostasis and maximize clinical benefits.