Immune Netw.  2009 Aug;9(4):122-126. 10.4110/in.2009.9.4.122.

Regulation of Tumor Immune Surveillance and Tumor Immune Subversion by TGF-beta

• Park HY
• Wakefield
• Mamura M

• KMID: 1474583
• DOI: http://doi.org/10.4110/in.2009.9.4.122

Abstract

Transforming growth factor-beta (TGF-beta) is a highly pleiotropic cytokine playing pivotal roles in immune regulation. TGF-beta facilitates tumor cell survival and metastasis by targeting multiple cellular components. Focusing on its immunosuppressive functions, TGF-beta antagonists have been employed for cancer treatment to enhance tumor immunity. TGF-beta antagonists exert anti-tumor effects through #1 activating effector cells such as NK cells and cytotoxic CD8+ T cells (CTLs), #2 inhibiting regulatory/suppressor cell populations, #3 making tumor cells visible to immune cells, #4 inhibiting the production of tumor growth factors. This review focuses on the effect of TGF-beta on T cells, which are differentiated into effector T cells or newly identified tumor-supporting T cells.

Keyword

transforming growth factor-beta (TGF-beta); primary tumor; metastasis; CD8+T cells; IL-17

MeSH Terms

Cell Survival
Intercellular Signaling Peptides and Proteins
Interleukin-17
Killer Cells, Natural
Neoplasm Metastasis
T-Lymphocytes
Transforming Growth Factor beta
Intercellular Signaling Peptides and Proteins
Interleukin-17
Transforming Growth Factor beta

Figure

• 

  Figure 1 TGF-β down-regulates the expression of NKG2D on CD8+ T cells and NKG2D ligand on tumor cells.

• 

  Figure 2 The role of TGF-β in subverting the CD8+ T cell response. TGF-β produced and activated in the tumor environment suppresses the immune surveillance, which mainly affects the number of metastasis by preventing the generation of cytotoxic T cells. On the other hand, TGF-β in combination with other factors, such as IL-6, subverts CD8+ T cells into IL-17 producing cells, which mainly affects the size of tumor and metastasis. IL-17 might promote survival of tumor cells in the condition with low nutrition or chemotherapy.

• 

  Figure 3 The role of TGF-β in subverting the CD4+ T cell response. TGF-β directly or indirectly suppresses cytotoxic T cells via the suppression of CD4+ Th1 cells. TGF-β, presumably in combination with other factors, subverts CD4+ T cells into Foxp3+ Tregs or Th17 cells.

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