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TGFβ in T cell biology and tumor immunity: Angel or devil?
Eric Tu1, Pei Zhi Cheryl Chia1, Wanjun Chen1
1Mucosal Immunology Section, OPCB, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract:
The evolutionally conserved transforming growth factor β (TGFβ) affects multiple cell types in the immune system by either stimulating or inhibiting their differentiation and function. Studies using transgenic mice with ablation of TGFβ or its receptor have revealed the biological significance of TGFβ signaling in the control of T cells. However, it is now clear that TGFβ is more than an immunosuppressive cytokine. Disruption of TGFβ signaling pathway also leads to impaired generation of certain T cell populations. Therefore, in the normal physiological state, TGFβ actively maintains T cell homeostasis and regulates T cell function. However, in the tumor microenvironment, TGFβ creates an immunosuppressive milieu that inhibits antitumor immunity. Here, we review recent advances in our understanding of the roles of TGFβ in the regulation of T cells and tumor immunity.
Insights
Transforming growth factor β (TGFβ) is crucial for T cell homeostasis and function. However, in tumors, TGFβ suppresses the immune response, inhibiting anti-tumor immunity.
Area of Science:
- Immunology
- Cell Biology
- Cancer Research
Background:
- Transforming growth factor β (TGFβ) is an evolutionarily conserved cytokine with diverse roles in the immune system.
- TGFβ signaling influences T cell differentiation and function, impacting immune responses.
- While known for immunosuppression, TGFβ also plays a role in T cell generation and homeostasis.
Purpose of the Study:
- To review recent advances in understanding TGFβ's role in T cell regulation.
- To explore TGFβ's dual function in normal physiology and the tumor microenvironment.
- To highlight TGFβ's impact on antitumor immunity.
Main Methods:
- Review of existing literature on TGFβ signaling in T cells.
- Analysis of studies involving transgenic mice with TGFβ pathway disruptions.
- Examination of TGFβ's role in the tumor microenvironment.
Main Results:
- TGFβ is essential for maintaining T cell homeostasis and regulating T cell function.
- Disruption of TGFβ signaling can impair the generation of specific T cell populations.
- In the tumor microenvironment, TGFβ promotes an immunosuppressive milieu, hindering anti-tumor immunity.
Conclusions:
- TGFβ has complex and context-dependent roles in T cell immunity.
- Understanding TGFβ's dual nature is critical for developing effective cancer immunotherapies.
- Targeting TGFβ signaling may offer therapeutic strategies to enhance anti-tumor responses.
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