Year: 2015
Type: article
Abstract: Thus, the GVHD seen in this report is quite unexpected.Possible factors in the current report that may help explain the unexpected GVHD rates include the timing of NK-cell infusion (8-35 days after transplant), the lack of posttransplant immunosuppression, or the hyperactivation of the NK cells, which were expanded on interleukin 15-secreting feeder cells.It is important to note that all 4 patients receiving unrelated donor transplants developed GVHD compared with only 1 of 5 patients receiving related donor transplants, further implicating a T-cell etiology mediated by minor antigens that was somehow exacerbated by the infused NK cells.This then raises several possible mechanisms to explain the observed GVHD.As shown in the figure, subclinical dermal or mucosal inflammation may increase stress ligands, rendering epithelium susceptible to recognition by NK cells, causing (1) a direct effect via lysis or indirect activation of adaptive immunity through (2) cytokine-mediated upregulation of HLA for T-cell recognition, (3) stimulation of cytotoxic T cells, (4) activation of helper T cells, or (5) maturation of dendritic cells for enhanced antigen presentation or crosspresentation.Whichever the case, these findings force us to recognize the potential potency of NK cells and to consider that GVL is no longer discretely separated from GVHD for NK cells.Further understanding of this mechanism is essential for understanding GVHD and the future of adoptive cell therapy with NK cells.Conflict-of-interest disclosure: The author declares no competing financial interests.n
Source: Blood
Author: Shaji Kumar
Institution: Mayo Clinic
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2008086115