Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, WA, United States.
Front Immunol. 2021 Apr 22;12:652105. doi: 10.3389/fimmu.2021.652105. eCollection 2021.
Transplantation of allogeneic hematopoietic cells faces two barriers: failure of engraftment due to a host versus graft reaction, and the attack of donor cells against the patient, the graft versus host (GVH) reaction. This reaction may lead to GVH disease (GVHD), but in patients transplanted due to leukemia or other malignant disorders, this may also convey the benefit of a graft versus leukemia (GVL) effect. The interplay of transplant conditioning with donor and host cells and the environment in the patient is complex. The microbiome, particularly in the intestinal tract, profoundly affects these interactions, directly and via soluble mediators, which also reach other host organs. The microenvironment is further altered by the modifying effect of malignant cells on marrow niches, favoring the propagation of the malignant cells. The development of stable mixed donor/host chimerism has the potential of GVHD prevention without necessarily increasing the risk of relapse. There has been remarkable progress with novel conditioning regimens and selective T-cell manipulation aimed at securing engraftment while preventing GVHD without ablating the GVL effect. Interventions to alter the microenvironment and change the composition of the microbiome and its metabolic products may modify graft/host interactions, thereby further reducing GVHD, while enhancing the GVL effect. The result should be improved transplant outcome.
由于宿主对移植物的反应而导致植入失败，以及供体细胞对患者的攻击，即移植物抗宿主反应（GVHD）。这种反应可能导致 GVHD，但对于因白血病或其他恶性疾病而接受移植的患者，这也可能带来移植物抗白血病（GVL）效应的益处。移植预处理与供体细胞和宿主细胞以及患者体内环境的相互作用非常复杂。微生物组，特别是在肠道中，直接并通过可溶性介质，对这些相互作用产生深远影响，这些介质也会到达其他宿主器官。恶性细胞对骨髓龛的修饰作用进一步改变了微环境，有利于恶性细胞的增殖。稳定的混合供体/宿主嵌合体的发展有可能预防 GVHD，而不必增加复发的风险。新型预处理方案和选择性 T 细胞操作的发展取得了显著进展，旨在在不消除 GVL 效应的情况下确保植入，同时预防 GVHD。改变微环境和改变微生物组及其代谢产物组成的干预措施可能会改变移植物/宿主的相互作用，从而进一步降低 GVHD，同时增强 GVL 效应。其结果应该是改善移植结果。
