The success of both, solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) requires a sound balance between alloreactivity and tolerance. SOT and HSCT could only become standard therapies for many end-stage organ diseases or severe hematological malignancies thanks to the development of modern immunosuppressive strategies, which enable to transform T and NK cell allorecognition of genetic disparities between donor and recipient into tolerance. Tolerance induction by immune suppressants is a prerequisite to prevent acute or chronic graft rejection in SOT and to avoid graft-versus-host disease (GvHD) in HSCT. However, keeping an individual balance between a sufficient alloimmune tolerance and maintenance of adequate immune defense against infections and relapse continues to be a major challenge in transplantation.
In this situation, the role of immune checkpoints pathways (iCP) is of superior interest. The activation of iCP by the interaction of a co-inhibitory receptor with its cognate ligand is essential for maintaining immune homeostasis, diminishing tissue damage, and preventing unwanted autoimmunity. The dysregulation of iCP molecules can result in immune escape from host immune defense in infection and cancer.
Besides cytotoxic T lymphocyte protein-4 (CTLA-4) and programmed cell death protein-1 (PD-1), a number of novel co-inhibitory receptors with corresponding binding partners have been discovered in recent years like lymphocyte activation gene 3 (LAG-3) and Human leukocyte antigen class II, T-cell immunoglobulin mucin-3 (TIM-3) and galectin-9, Leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) and HLA-G, and so on. Importantly, co-inhibitory receptors share distinct signaling motifs. Thus, molecules of iCP provide a functional repertoire to counteract T and NK cell immune responsiveness by different signaling pathways.
Under physiological conditions, iCP molecules are expressed with a low expression intensity in tissues and blood cells but are up-regulated upon stimulation. Most iCP molecules can be released into circulation as soluble molecules or via extracellular vesicles. Local inflammatory signals, genetic variations within the 3’- or 5’-untranslated regions, and within the coding region play an important role in the expression or functionality of iCP molecules.
In transplantation, there is accumulating evidence that networking of iCP molecules influence the transplantation outcome with respect to both extremes: low tolerance and uncontrolled alloreactivity leading to graft rejection in SOT or GvHD in HSCT; exaggerated tolerance and insufficient alloreactivity leading to relapses in HSCT for hematological malignancies. In this Research Topic, we welcome Reviews and Original Research articles highlighting the contribution of immune checkpoint molecules to allograft tolerance or to the clinical outcome of SOT as well as HSCT.
We welcome the submission of Original Research articles, Reviews, and Mini-Reviews covering, but not limited to, the following sub-topics:
1. Genetic aspects of immune checkpoints in SOT and/or HSCT
2. Expression of immune checkpoints on immune cells, in tissues or as soluble molecules
3. The role of extracellular vesicles in immune checkpoints communication
4. Biomarkers indicating the role of immune checkpoints in SOT and/or HSCT
5. The interaction of immune suppressants and immune checkpoints in SOT and/or HSCT
6. The influence of immune checkpoints on relapse or GvHD in HSCT
The success of both, solid organ transplantation (SOT) and hematopoietic stem cell transplantation (HSCT) requires a sound balance between alloreactivity and tolerance. SOT and HSCT could only become standard therapies for many end-stage organ diseases or severe hematological malignancies thanks to the development of modern immunosuppressive strategies, which enable to transform T and NK cell allorecognition of genetic disparities between donor and recipient into tolerance. Tolerance induction by immune suppressants is a prerequisite to prevent acute or chronic graft rejection in SOT and to avoid graft-versus-host disease (GvHD) in HSCT. However, keeping an individual balance between a sufficient alloimmune tolerance and maintenance of adequate immune defense against infections and relapse continues to be a major challenge in transplantation.
In this situation, the role of immune checkpoints pathways (iCP) is of superior interest. The activation of iCP by the interaction of a co-inhibitory receptor with its cognate ligand is essential for maintaining immune homeostasis, diminishing tissue damage, and preventing unwanted autoimmunity. The dysregulation of iCP molecules can result in immune escape from host immune defense in infection and cancer.
Besides cytotoxic T lymphocyte protein-4 (CTLA-4) and programmed cell death protein-1 (PD-1), a number of novel co-inhibitory receptors with corresponding binding partners have been discovered in recent years like lymphocyte activation gene 3 (LAG-3) and Human leukocyte antigen class II, T-cell immunoglobulin mucin-3 (TIM-3) and galectin-9, Leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) and HLA-G, and so on. Importantly, co-inhibitory receptors share distinct signaling motifs. Thus, molecules of iCP provide a functional repertoire to counteract T and NK cell immune responsiveness by different signaling pathways.
Under physiological conditions, iCP molecules are expressed with a low expression intensity in tissues and blood cells but are up-regulated upon stimulation. Most iCP molecules can be released into circulation as soluble molecules or via extracellular vesicles. Local inflammatory signals, genetic variations within the 3’- or 5’-untranslated regions, and within the coding region play an important role in the expression or functionality of iCP molecules.
In transplantation, there is accumulating evidence that networking of iCP molecules influence the transplantation outcome with respect to both extremes: low tolerance and uncontrolled alloreactivity leading to graft rejection in SOT or GvHD in HSCT; exaggerated tolerance and insufficient alloreactivity leading to relapses in HSCT for hematological malignancies. In this Research Topic, we welcome Reviews and Original Research articles highlighting the contribution of immune checkpoint molecules to allograft tolerance or to the clinical outcome of SOT as well as HSCT.
We welcome the submission of Original Research articles, Reviews, and Mini-Reviews covering, but not limited to, the following sub-topics:
1. Genetic aspects of immune checkpoints in SOT and/or HSCT
2. Expression of immune checkpoints on immune cells, in tissues or as soluble molecules
3. The role of extracellular vesicles in immune checkpoints communication
4. Biomarkers indicating the role of immune checkpoints in SOT and/or HSCT
5. The interaction of immune suppressants and immune checkpoints in SOT and/or HSCT
6. The influence of immune checkpoints on relapse or GvHD in HSCT
