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Cytotoxic Pathways in Allogeneic Hematopoietic Cell Transplantation

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for hematologic malignancies, and other hematologic and immunologic diseases. Donor-derived immune cells identify and attack cancer cells in the patient producing a unique graft-vs.-tumor (GVT) effect. This...

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Detalles Bibliográficos
Autores principales: Du, Wei, Cao, Xuefang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315278/
https://www.ncbi.nlm.nih.gov/pubmed/30631325
http://dx.doi.org/10.3389/fimmu.2018.02979
Descripción
Sumario:Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for hematologic malignancies, and other hematologic and immunologic diseases. Donor-derived immune cells identify and attack cancer cells in the patient producing a unique graft-vs.-tumor (GVT) effect. This beneficial response renders allo-HCT one of the most effective forms of tumor immunotherapy. However, alloreactive donor T cells can damage normal host cells thereby causing graft-vs.-host disease (GVHD), which results in substantial morbidity and mortality. To date, GVHD remains as the major obstacle for more successful application of allo-HCT. Of special significance in this context are a number of cytotoxic pathways that are involved in GVHD and GVT response as well as donor cell engraftment. In this review, we summarize progress in the investigation of these cytotoxic pathways, including Fas/Fas ligand (FasL), perforin/granzyme, and cytokine pathways. Many studies have delineated their distinct operating mechanisms and how they are involved in the complex cellular interactions amongst donor, host, tumor, and infectious pathogens. Driven by progressing elucidation of their contributions in immune reconstitution and regulation, various interventional strategies targeting these pathways have entered translational stages with aims to improve the effectiveness of allo-HCT.