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Front. Immunol. | doi: 10.3389/fimmu.2018.02979

Cytotoxic pathways in allogeneic hematopoietic cell transplantation

  • 1Roswell Park Comprehensive Cancer Center, University at Buffalo, United States
  • 2University of Maryland, Baltimore, United States

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-versus-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-versus-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.

Keywords: Allogeneic hematopoietic cell transplantation (allo-HCT), Graft-versus-host disease (GVHD), Graft-versus-tumor (GVT) effect, cytotoxic pathways, the Fas/Fas ligand (FasL) system, the perforin/granzyme pathway, Cytokines

Received: 05 Sep 2018; Accepted: 04 Dec 2018.

Edited by:

Xue-Zhong Yu, Medical University of South Carolina, United States

Reviewed by:

Ralf Dressel, University Medical Center Göttingen, Germany
Tomomi Toubai, Yamagata University, Japan  

Copyright: © 2018 Du and CAO. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. XUEFANG CAO, University of Maryland, Baltimore, Baltimore, United States, xuefangcao@som.umaryland.edu