Immune Mediators As Therapeutic Targets in Gvhd; Cytokines, Growth Factors, Chemokines, and Co-Stimulation /Co-Inhibition Publisher Pubmed



Rastegari A ; Mohebbi F
Source: Transplant Immunology Published:2025

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) and emerging allogeneic T cell–based immunotherapies offer curative potential for hematologic malignancies, solid tumors, and selected non-malignant disorders through graft-versus-tumor (GvT) and immune reconstitution effects mediated by donor immune cells. However, their clinical success is constrained by graft-versus-host disease (GvHD) and other immune-mediated toxicities resulting from donor–host alloreactivity. Therefore, a central challenge is to develop personalized, safer allogeneic cellular therapies that preserve potent anti-tumor and immune-restorative functions while minimizing tissue injury. This review integrates the current understanding of acute and chronic GvHD immunopathogenesis, covering cytokine and chemokine networks, growth-factor signaling, and co-stimulatory/co-inhibitory pathways, and links these mechanisms to therapeutic strategies for selective immune modulation. Drawing on translational insights, we propose a framework for next-generation allogeneic cell-based therapies that are precision-tuned to donor/recipient biology, advancing individualized anticancer and immune-reconstitution outcomes with improved safety. © 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.