Background:Donor lymphocyte infusion (DLI) is employed to enhance the graft-versus-leukemia (GvL) effect and improve remission rates following allogeneic hematopoietic cell transplantation (alloHCT). However, graft-versus-host disease (GvHD) remains a significant complication of both alloHCT and DLI. Regular exercise has been shown to reduce cancer risk, enhance treatment responses, and mitigate therapy-related toxicities. This study investigated the effects of voluntary wheel running on GvL and GvHD following DLI in a xenogeneic mouse model.Methods:Immunodeficient NSG-IL15 mice were challenged with a luciferase-expressing chronic myelogenous leukemia cell line (K562), and then they received DLI with peripheral blood mononuclear cells (PBMCs) from healthy volunteers (GvL model). Non-tumor bearing mice received DLI to model GvHD. Half of the mice in each group were then given free access to a running wheel. Tumor growth (bioluminescence), GvHD, and body weight were monitored biweekly for ~40 days.Results:In the GvHD model, exercise extended overall survival by 60% and reduced GvHD severity. In the GvL model, exercise significantly lowered tumor burden and extended tumor-free survival in both DLI and vehicle control groups by 44.5% and 37.5%, respectively, suggesting both immune-dependent and immune-independent mechanisms. RNA sequencing of bone marrow from saline-injected mice revealed that genes associated with mitochondrial function, protein synthesis, and metabolic processes were downregulated in tumors from exercised mice.Conclusions:In summary, voluntary wheel running improved DLI outcomes by enhancing GvL and reducing GvHD. These benefits may be mediated, in part, through exercise-induced metabolic reprogramming of leukemia cells.
背景：供体淋巴细胞输注（DLI）被用于增强移植物抗白血病（GvL）效应并提高异基因造血细胞移植（alloHCT）后的缓解率。然而，移植物抗宿主病（GvHD）仍然是alloHCT和DLI的重要并发症。规律运动已被证明可降低癌症风险、增强治疗反应并减轻治疗相关毒性。本研究在异种移植小鼠模型中探讨了自主跑轮运动对DLI后GvL和GvHD的影响。 方法：用表达荧光素酶的慢性髓系白血病细胞系（K562）攻击免疫缺陷NSG-IL15小鼠，随后输注来自健康志愿者的外周血单个核细胞（PBMCs）进行DLI（GvL模型）。非荷瘤小鼠接受DLI以模拟GvHD。每组中一半小鼠被给予自由跑轮条件。在约40天内，每两周监测一次肿瘤生长（生物发光）、GvHD和体重变化。 结果：在GvHD模型中，运动使总生存期延长了60%并降低了GvHD严重程度。在GvL模型中，运动显著降低了肿瘤负荷，并在DLI组和载体对照组中分别将无瘤生存期延长了44.5%和37.5%，提示存在免疫依赖性和免疫非依赖性双重机制。对盐水注射小鼠骨髓的RNA测序显示，运动组小鼠肿瘤中与线粒体功能、蛋白质合成及代谢过程相关的基因表达下调。 结论：综上所述，自主跑轮运动通过增强GvL效应和减轻GvHD改善了DLI的疗效。这些益处可能部分通过运动诱导的白血病细胞代谢重编程介导。
肿瘤(癌症)患者之家