Table 1 Different Th subsets and their function in the TME
From: Th17 cell function in cancers: immunosuppressive agents or anti-tumor allies?
Th subsets | Transcription factors | Differentiation cytokines | Effector molecules | Main functions in the TME | Clinical relevance | Refs |
|---|---|---|---|---|---|---|
Th1 | STAT4, T-bet | IL-12, IFN-Υ | IFN-γ, cytolytic enzymes (e.g., perforin, granzymes) | Promote anti-tumor immunity by activating cytotoxic T cells and macrophages, inhibit tumor angiogenesis | Th1 cells have been linked to a positive outlook in different types of cancer due to their ability to produce molecules that can directly eliminate cancer cells and hinder the formation of new blood vessels | |
Th2 | STAT6, GATA3 | IL-4 | IL-4, IL-5, IL-13, TGF-β, matrix metalloproteinases | Promote tumor growth and metastasis by inducing immunosuppressive mechanisms, angiogenesis, and tissue remodeling | Th2 cells have been linked to unfavorable outcomes in numerous types of cancer due to their ability to produce molecules that support tumor progression, metastasis, and suppression of the immune system | |
Th9 | STAT6, PU-1, IRF4, BATF | IL-4, TGF-β | IL-9, granzymes, perforin | Enhance anti-tumor immunity by recruiting and activating cytotoxic cells, inhibit tumor angiogenesis | Th9 cells have demonstrated encouraging anti-tumor properties in preclinical studies, however, their significance in clinical settings is currently under scrutiny | |
Th17 | STAT3, RORγt | IL-1, IL-23, IL-6, TGF-β | IL-17, IL-22, matrix metalloproteinases, angiogenic factors | Promote tumor growth and metastasis by inducing inflammation, angiogenesis, and immunosuppression Inhibit tumor progression by recruiting different mechanisms | Th17 cells can have both pro-tumor and anti-tumor effects, depending on the specific context and balance of their effector molecules | |
Th22 | STAT3, AhR, RORγt, RUNX3 | IL-6, TNF-α | IL-22, matrix metalloproteinases, angiogenic factors | Promote tumor growth and metastasis by inducing tissue remodeling, angiogenesis, and immunosuppression | Th22 cells are associated with poor prognosis in in numerous types of cancer due to their ability to produce molecules that support tumor growth, metastasis, and immunosuppression | |
Treg | STAT6, FOXP3 | IL-2, TGF-β | IL-10, TGF-β | Suppress anti-tumor immune responses, promote tumor growth and metastasis | Tregs have been linked to unfavorable outcomes in numerous types of cancer due to their ability to inhibit anti-tumor immune reactions and facilitate the advancement of tumors. | |
Tfh | STAT3, Bcl6, ASCL2 | IL-6 | IL-21 | Promote B cell-mediated anti-tumor immunity, but can also induce immunosuppression | The effects of Tfh cells on tumors can vary, as they have the potential to either promote or inhibit tumor growth, depending on the specific context and the balance of their effector molecules. |