Year: 2020
Type: review
Abstract: Allogeneic hematopoietic stem cell transplantation (allo-HCT) holds curative potential for many hematological disorders. However, the pathophysiology of the desired graft-versus-tumor effect is linked to life-threatening complications of acute graft-versus-host disease (GVHD). Allogeneic donor T lymphocytes are essential for causing GVHD, and their activation relies on the coordination of TCR engagement and co-stimulation, also known as Signal 1 and Signal 2. In addition to these signals, a network of secreted cytokines by immune cells provides a third signal, Signal 3, that is critical for the initiation and maintenance of GVHD. Strategies to target Signal 3 in human diseases have shown therapeutic benefit for inflammatory disorders such as Rheumatoid Arthritis and Inflammatory Bowel Disease. However, despite our growing understanding of their role in GVHD, the success of targeting individual cytokines has been modest with some notable exceptions. This review aims to describe current approaches toward targeting Signal 3 in clinical GVHD, and to highlight emerging studies in immune cell biology that may be harnessed for better clinical translation.
Source: Frontiers in Immunology
Authors: Stephanie Kim, Pavan Reddy
Institutions: University of Michigan, Michigan Medicine
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,950
Awards: G1362039589, Michigan Medical Scientist Training Program, G2855199646, Development of novel strategy for treatment of steroid refractory GVHD, Targeting Novel DAMP mediated signaling pathways to mitigate GVHD, Role of COPII Vesicles in T cell immunity, Cellular and molecular mechanisms of target tissue resistance for mitigating GVHD severity
OpenAlex ID: W3022887434