Tregs play an important role in preventing autoimmune diseases and maintaining self-tolerance. However, their implications in cancer are complex. High Treg numbers in the tumor microenvironment are associated with poor prognosis, as they suppress tumor immunity while also having a role in promoting anti-tumor effects. The balance between pro-tumor and anti-tumor effects of Tregs depends on the specific tumor type, stage, and individual patient. Researchers are actively studying ways to modulate Treg activity to enhance or suppress the immune response in a wide variety of disorders.

Tregs in Autoimmunity

Treg cells can suppress immune responses to self-antigens, safeguarding against autoimmunity, and have also been shown to hinder effective cancer immunotherapies. Dysregulated Treg activity has been linked to the development of several autoimmune diseases. Specifically, Treg function and frequency are often compromised in autoimmune diseases like multiple sclerosis (MS), rheumatoid arthritis (RA), or systemic lupus erythematosus (SLE)^2-5.

In addition to Treg dysfunction, there’s evidence that immunoregulatory mechanisms fail to control autoreactive T cells due to reduced responsiveness of T effector cells to the suppressive effects of Tregs.

Treg cells have been shown to demonstrate plasticity, which includes the loss of FOXP3 expression. This leads to the emergence of “ex-Treg” cells and “fragile” Treg cells. Ex-Treg cells lose FOXP3 expression and may contribute to inflammatory responses, while fragile Treg cells retain FOXP3 expression but engage in an inflammatory program, compromising their suppressive activity.

A deeper understanding of Treg function could present a promising strategy for managing chronic inflammation in autoimmune disorders.

Tregs in Transplantation

In graft versus host disease (GVHD), the host immune system rejects donor lymphocytes due to differences in major histocompatibility complexes. Tregs are commonly known to induce tolerance in a host, but have also been shown as effective in limiting allogeneic responses and prevent GVHD for extended periods of time. While Tregs have shown strong potential in controlling GVHD, therapeutic approaches continue to require optimization, as Treg stability and the generation of sufficient Treg numbers for treatment remain problematic to solve⁶.

Treg Pathways

Visit our Pathways Library for detailed interactive pathways, including our Regulatory T Cells poster containing information on Treg development and mechanisms of action. 

References

1. Hosseinalizadeh, Hamed et al. “Regulating the regulatory T cells as cell therapies in autoimmunity and cancer.” Frontiers in medicine vol. 10 1244298. 27 Sep. 2023, doi:10.3389/fmed.2023.1244298

2. La Cava, Antonio. “Natural Tregs and autoimmunity.” Frontiers in bioscience (Landmark edition) vol. 14,1 333-43. 1 Jan. 2009, doi:10.2741/3247

3. Romano, Marco et al. “Past, Present, and Future of Regulatory T Cell Therapy in Transplantation and Autoimmunity.” Frontiers in immunology vol. 10 43. 31 Jan. 2019, doi:10.3389/fimmu.2019.00043

4. Slobodin, Gleb, and Doron Rimar. “Regulatory T Cells in Systemic Sclerosis: a Comprehensive Review.” Clinical reviews in allergy & immunology vol. 52,2 (2017): 194-201. doi:10.1007/s12016-016-8563-6

5. Zhang, Yuyue et al. “Differences in Maturation Status and Immune Phenotypes of Circulating Helios+ and Helios- Tregs and Their Disrupted Correlations With Monocyte Subsets in Autoantibody-Positive T1D Individuals.” Frontiers in immunology vol. 12 628504. 12 May. 2021, doi:10.3389/fimmu.2021.628504

6. Guo, Wen-Wen et al. “Regulatory T Cells in GVHD Therapy.” Frontiers in immunology vol. 12 697854. 18 Jun. 2021, doi:10.3389/fimmu.2021.697854