The multifaceted role of Th17 lymphocytes and their associated cytokines in cancer

Abstract

While the role of T helper 17 lymphocytes (Th17) in the pathogenesis of autoimmune diseases and in infectious immunity has been relatively well defined, the impact of these cells and their associated cytokines on cancer development is still under debate. Although multiple reports have indicated that Th17 can promote anticancer immunity, others have argued that these cells may exhibit tumor-promoting properties. This dichotomy in the function of Th17 lymphocytes in cancer may be related to the versatile nature of these cells, being capable of differentiating into either proinflammatory Th1 or suppressive FoxP3-expressing Treg cells or hybrid T cell subsets depending on the underlying environmental conditions. In the current review, we examine the role of Th17 lymphocytes and Th17-associated cytokines in cancer and discuss how factors that control their final lineage commitment decision may influence the balance between their tumor-promoting versus tumor-suppressing properties.

Figure 1

Specific cytokines drive the differentiation of specialized T helper lymphocytes. Naïve CD4⁺ T lymphocytes, upon activation and in the presence of specific cytokines, differentiate into Th1, Th2, Th17, or Treg. The plasticity of Th17 and Treg enables them to transdifferentiate into Th17/Treg subsets. Th17 cells can also acquire a Th1-type phenotype leading to “hybrid” Th17/Th1 cells. The nature and concentration of the cytokines present in the differentiation milieu lead to the activation of distinct signaling cascades and transcription factors which control the developmental program of these specific lineages.

Figure 2

Pro-versus anti-tumoral effects of Th17 lymphocytes and the cytokines they produce on cancer development. Th17 lymphocytes produce cytokines which may promote or impair tumor development. Depending on the microenvironment Th17 may differentiate into Th1 or hybrid lymphocytes capable of controlling tumor growth or into protumoral Treg. IDO: indoleamine 2,3-dioxygenase.