Hematopoietic Stem Cell Transplantation (HSCT) is a highly curative therapy for many patients with hematological malignancies. In this setting, the desired outcome relies on the allo-reactivity of donor-derived lymphocytes towards malignant cells in the patient. Such reactivity is termed graft versus leukemia (GVL) effect, and is responsible for controlling the malignancy. However, GVL is often accompanied by a widespread allo-reactivity against healthy tissues of the patient, resulting in a common post-transplant complication termed graft versus host disease (GVHD). Acute GVHD is an inflammatory process occurring early after transplant, mediated by lymphocytes infused in the graft. Chronic GVHD (cGVHD) occurs later, post-transplant and presents as auto-immune-like phenomena in multiple organs. It emerges from the self-reactivity of donor-derived T and B lymphocytes originating de novo after transplant. Chronic GVHD is associated with imbalances in immune tolerance mechanisms, whereby regulatory T cells (Treg) are thought to play a pivotal role.
Despite many advances in the understanding of GVHD pathogenesis leading to diverse therapeutic and prophylactic approaches, GVHD remains a major cause of non-relapse mortality after HSCT, requiring a fine balance between the therapeutic control of auto-immunity, GVL and immunity to pathogens. The prominent role played by Tregs in the control of autoimmunity in general and GVHD in particular, has led to various new therapies that modulate the Treg pool in the post-transplantation period, either directly through Treg infusions, or indirectly through therapies such as ruxolitinib and low dose IL-2. The promising data obtained thus far highlights the need to better understand the role of Treg kinetics after HSCT and the impact that manipulating the Treg pool can have in the prophylaxis and treatment of GVHD, as well as in the robustness of the GVL effect after HSCT.
In this Research Topic we aim to put together novel articles providing new insights into the role that Tregs play in GVHD. In addition, the development and clinical evaluation of novel strategies that modulate Treg to prevent or treat GVHD, while preserving immune responses against the original tumor and pathogens will be of great interest.
We welcome Original Research, Review, Mini Review and Opinion articles related, but not limited to, the following areas:
1. Treg function: role in the physiology of immune system and mechanisms of action
2. Treg reconstitution after allogeneic HSCT and identification of settings where Treg recovery is delayed or impaired.
3. Mechanisms of action of Treg and their role in the regulation of immune responses after HSCT
4. Molecular signatures and functions of Treg after HSCT
5. Studies characterizing Treg in tissues affected by GVHD
6. The role of Treg in infused stem cell products
7. The impact of Treg on graft versus tumor reactivity
8. Preclinical and clinical studies describing strategies that prevent or treat GVHD through infusion of Treg products or administration of Treg-modulating agents
9. Potential role of genetically modified Treg therapies for treatment and prevention of GVHD
Hematopoietic Stem Cell Transplantation (HSCT) is a highly curative therapy for many patients with hematological malignancies. In this setting, the desired outcome relies on the allo-reactivity of donor-derived lymphocytes towards malignant cells in the patient. Such reactivity is termed graft versus leukemia (GVL) effect, and is responsible for controlling the malignancy. However, GVL is often accompanied by a widespread allo-reactivity against healthy tissues of the patient, resulting in a common post-transplant complication termed graft versus host disease (GVHD). Acute GVHD is an inflammatory process occurring early after transplant, mediated by lymphocytes infused in the graft. Chronic GVHD (cGVHD) occurs later, post-transplant and presents as auto-immune-like phenomena in multiple organs. It emerges from the self-reactivity of donor-derived T and B lymphocytes originating de novo after transplant. Chronic GVHD is associated with imbalances in immune tolerance mechanisms, whereby regulatory T cells (Treg) are thought to play a pivotal role.
Despite many advances in the understanding of GVHD pathogenesis leading to diverse therapeutic and prophylactic approaches, GVHD remains a major cause of non-relapse mortality after HSCT, requiring a fine balance between the therapeutic control of auto-immunity, GVL and immunity to pathogens. The prominent role played by Tregs in the control of autoimmunity in general and GVHD in particular, has led to various new therapies that modulate the Treg pool in the post-transplantation period, either directly through Treg infusions, or indirectly through therapies such as ruxolitinib and low dose IL-2. The promising data obtained thus far highlights the need to better understand the role of Treg kinetics after HSCT and the impact that manipulating the Treg pool can have in the prophylaxis and treatment of GVHD, as well as in the robustness of the GVL effect after HSCT.
In this Research Topic we aim to put together novel articles providing new insights into the role that Tregs play in GVHD. In addition, the development and clinical evaluation of novel strategies that modulate Treg to prevent or treat GVHD, while preserving immune responses against the original tumor and pathogens will be of great interest.
We welcome Original Research, Review, Mini Review and Opinion articles related, but not limited to, the following areas:
1. Treg function: role in the physiology of immune system and mechanisms of action
2. Treg reconstitution after allogeneic HSCT and identification of settings where Treg recovery is delayed or impaired.
3. Mechanisms of action of Treg and their role in the regulation of immune responses after HSCT
4. Molecular signatures and functions of Treg after HSCT
5. Studies characterizing Treg in tissues affected by GVHD
6. The role of Treg in infused stem cell products
7. The impact of Treg on graft versus tumor reactivity
8. Preclinical and clinical studies describing strategies that prevent or treat GVHD through infusion of Treg products or administration of Treg-modulating agents
9. Potential role of genetically modified Treg therapies for treatment and prevention of GVHD
