Author:
Kwon Yong-Rim,Kim Hye Joung,Sohn Min-Jung,Lim Ji-Young,Park Kyung-Shin,Lee Seok,Chung Nack-Gyun,Jeong Dae-Chul,Min Chang-Ki,Kim Yoo-Jin
Abstract
Abstract
Background
Successful prevention of post-transplantation relapse after donor lymphocyte infusion (DLI) depends on its capability to mediate an effective graft-versus-leukemia (GVL) response while minimizing DLI-related toxicity, including graft-versus-host disease (GVHD).
Methods
We assessed the effects of decitabine (DEC), a hypomethylating agent, upon allogeneic immune reaction in a murine model of DLI.
Results
Significantly greater tumor growth retardation and survival prolongation occurred in mice administered with 1.0 mg/kg DEC for 5 days (DEC-1.0) than in control or DEC-0.1 mice. Upon prompt DEC and DLI co-administration, dendritic cells (DCs) were activated; DEC-1.0/DLI induced severe GVHD, and survival was significantly lower than with DLI alone or DEC-0.1/DLI treatments. IFN-γ and CD28 levels were higher in splenic DCs of DEC-1.0 mice than in those of control mice. Assessment of delayed DLI co-administration with DEC, when IFN-γ levels were normalized to control levels, revealed that DEC-1.0/DLI successfully facilitated tumor management without causing severe GVHD.
Conclusions
Our results suggest that DEC primes allogeneic immune reactions of DLI via DC activation, and GVHD and GVL effects are separable through optimal DLI timing based on DEC-induced increase in IFN-γ expression levels.
Funder
National Research Foundation of Korea
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,Hematology
Cited by
11 articles.
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