TNFR2 signaling modulates immunity after allogeneic hematopoietic cell transplantation |
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Affiliation: | 1. Research Service, St Louis Veterans Affairs Medical Center, St. Louis, MO;2. Division of Oncology, Washington University School of Medicine, St. Louis, MO;3. Division of Hematology, Mayo Clinic, Rochester, MN;4. Division of Oncology, Stanford Cancer Institute, CA;5. Centre for Lymphoid Cancer and Department of Medical Oncology, BC Cancer, Vancouver, BC;6. Divisions of Hematology/Oncology, UCLA, Los Angeles, CA;7. Divisions of Hematology/Oncology, University of Nebraska Medical Center, Omaha, NE;8. Divisions of Hematology/Oncology, Massachusetts General Hospital Cancer Center, Boston, MA;9. U Mass Memorial Cancer Center, Worcester, MA;10. Divisions of Hematology/Oncology, University of Chicago, Chicago, IL;11. Division of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY;12. Division of Hematologic Malignancies and Cellular Therapeutics, University of Kansas Cancer Center, Kansas City, KS |
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Abstract: | Tumor necrosis factor-α (TNF-α) signaling through TNF receptor 2 (TNFR2) plays a complex immune regulatory role in allogeneic hematopoietic cell transplantation (HCT). TNF-α is rapidly released in the circulation after the conditioning regimen with chemotherapy and/or radiotherapy. It activates the function of donor alloreactive T cells and donor Natural Killer cells and promotes graft versus tumor effects. However, donor alloreactive T cells also attack host tissues and cause graft versus host disease (GVHD), a life-threatening complication of HCT. Indeed, anti-TNF-α therapy has been used to treat steroid-refractory GVHD. Recent studies have highlighted another role for TNFR2 signaling, as it enhances the function of immune cells with suppressive properties, in particular CD4+Foxp3+ regulatory T cells (Tregs). Various clinical trials are employing Treg-based treatments to prevent or treat GVHD. The present review will discuss the effects of TNFR2 signaling in the setting of allogeneic HCT, the implications for the use of anti-TNF-α therapy to treat GVHD and the clinical perspectives of strategies that specifically target this pathway. |
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Keywords: | Tumor necrosis factor-α Tumor necrosis factor receptor 2 Allogeneic hematopoietic cell transplantation Graft versus tumor Graft versus host disease |
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