Innovative therapeutic strategies for GVHD treatment: immunotherapy and cell based therapies

GVHD remains as a serious and life-threatening complications after allogeneic hematopoietic stem cell transplantation (HSCT). It arises when donor T lymphocytes recognize host tissues as foreign and mount an immune response against them. Despite progress in prophylactic strategies and first-line immunosuppressive treatments, steroid-refractory GVHD continues to pose significant clinical challenges. In recent years, advances in immunomodulatory and cell-based therapies have opened new therapeutic avenues and improved outcomes for affected patients. Among the most promising innovations the use of Janus kinase (JAK) inhibitors, particularly ruxolitinib, which block inflammatory signaling pathways and have shown considerable efficacy in patients with steroid-resistant GVHD. In addition, cellular therapies such as T regulatory cells (Tregs) and mesenchymal stromal cells (MSCs) are being explored in clinical trials for their potential to restore immune tolerance and mitigate tissue damage through immunoregulatory mechanisms. Biologic agents targeting specific immune checkpoints and cytokine receptors such as abatacept (CTLA-۴-Ig) and anti-IL-۶R antibodies further expand the therapeutic landscape in this field. Monoclonal antibodies targeting specific immune receptors such as anti-IL-۲R and anti-CCR۵ have also shown potential in modulating the alloreactive immune response. Moreover, increasing attention has been paid to the role of the gut microbiome in GVHD pathogenesis. Fecal microbiota transplantation (FMT), aimed at restoring microbial diversity, is emerging as a novel adjunct therapy with encouraging early results. In conclusion, not only the integration of advanced immunotherapies, cell-based interventions, and microbiome-focused treatments marks a transformative era in GVHD management, but also strive to preserve the beneficial graft-versus-leukemia (GvL) effect.