The Therapeutic Strategies of Regulatory T Cells in Malignancies and Stem Cell Transplantations

Abstract

Regulatory T cells (Treg cells) are considered one of the main dynamic cell types within the immune system. Because Treg cells suppress immune responses, they have potential roles in immunological self-tolerance and may help to maintain immune homeostasis. Promoting Treg cell function and increasing their numbers might be useful in treating autoimmune disorders, as well as preventing allograft rejection. However, studies of mice and humans demonstrate that Treg cells promote cancer progression and suppress antitumor immunity. Therefore, suppressing Treg cell function or reducing their numbers could support the immune system's response to pathogenic microorganisms and tumors. As a result, there is great interest in investigating the Treg cells role in the treatment of hematological and nonhematological malignancies. Consequently, Treg cells could be a fundamentally important target for pathologies of the immune system. Targeting effector Treg cells could help to distinguish and selectively decrease these cells while preserving other Treg cells needed to suppress autoimmunity. Currently, a promising way to treat malignancies and other autoimmune disorders is stem cell transplantation. Stem cell transplants (SCT) can help to manage the production of Treg cells and also may produce more efficient Treg cells, thereby suppressing clinical disease progression. Specifically, mature T cells within the engrafted stem cells mediate this SCT beneficial effect. During SCT, the recipient's immune system is replaced with a donor, which allows for improved immune system function. In addition, SCT can protect from disease relapse, as graft-versus-host disease (GvHD) in transplant patients can be protective against cancer recurrence. The current review will define the role of regulatory T cells in treatment of malignancy. Additionally, it will summarize current promising research regarding the utility of regulatory T cells in stem cell transplantation.

β2-Adrenergic receptor activation on donor cells ameliorates acute GvHD

“…However, cutaneous aGvHD is associated with expansion of tissue-localized Th1, not Th17 cells (12), and T cell RORγt expression (Th17 transcription factor) exacerbates aGvHD (13,14). Tregs ameliorate aGvHD severity (15)(16)(17)(18), critical to the control of the immunopathology mediated by inflammatory T cells (19). There is an imbalance in inflammatory T cells and Tregs in aGvHD target organs (18,20).…”

The Role of TLRs in Anti-cancer Immunity and Tumor Rejection

“…Infiltration of a large number of Tregs into the tumor is often associated with poor prognosis and their removal can evoke and enhance anti-cancer immune response (102). On the other hand, systemic depletion of Tregs may elicit autoimmune diseases and the presence of Tregs is necessary for allograft survival (103). TLR ligands have been shown to block the suppressive effects of Tregs (104, 105).…”

Optimizing Blood Stem Cell Transplants Through Cellular Engineering

“…Treg cells have also been explored as a potential treatment to improve the outcomes of HSCTs by treating or preventing GvHD. However, a significant limitation of Treg cells treatment is that they suppress antitumor immunity, thereby inhibiting cancer treatment [51][52][53][54][55][56] . Treg cells are a type of CD4+ T cells that express the transcription factor Forkhead box P3 (FoxP3) and are involved in the suppression of immune responses against both self-and non-self -antigens.…”

“…These results indicate the potential for Treg treatment to be used to prevent the development of GvHD in post-HSCT patients. However, the ability of Tregs to support tumor progression and suppress anti-tumor immunity means that further research is needed to develop a safer Treg treatment 51 .…”