The contribution of the intestinal microbiome to immune recovery after HCT.
The contribution of the intestinal microbiome to immune recovery after HCT.
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DOI：
10.3389/fimmu.2022.988121
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发表时间：
2022
影响因子：
7.3
通讯作者：
Markey, Kate A.
中科院分区：
文献类型：
--
作者：
Wolfe, Alex E.;Markey, Kate A.
关键词：
异基因造血干细胞移植（allo-HCT）是一种治疗高危恶性血液病和免疫缺陷的免疫疗法。Allo-HCT具有治疗相关死亡率（TRM）的高风险，主要是由于感染或移植物抗宿主病（GVHD）。稳健的免疫恢复对于最佳患者结局至关重要，因为免疫学移植物抗白血病效应可防止复发，并且预防和控制感染都需要功能性先天免疫和适应性免疫。最简单地说，我们通过计数循环中的供体淋巴细胞亚群来测量免疫恢复。在功能方面，理想的免疫恢复更难定义，目前的实验室技术仅限于测量特定的疫苗反应或离体有丝分裂原。临床上，免疫功能低下表现为病毒、细菌和真菌生物体的问题性感染。此外，理想的恢复性免疫系统能够发挥移植物抗肿瘤效应以防止复发，并且不会诱导移植物抗宿主病。大型临床观察性研究已经将肠道微生物组内多样性的丧失与不良移植结果联系起来，包括总生存率降低和急性和慢性GVHD增加。此外，肠道微生物群落和淋巴细胞数量恢复之间的相关性现在已经使用多种方法进行了报道。大量临床可用的白色血细胞计数数据、淋巴细胞亚群的临床流式细胞术和设计用于捕获微生物群特异性T细胞（例如粘膜相关的不变T细胞、gd T细胞亚群）的定制流式细胞术分析都已被用于试图理解HCT患者中微生物群与恢复中的免疫系统之间的联系。此外，临床前研究表明，细菌代谢产物（包括丁酸盐、二级胆汁酸和色氨酸代谢产生的吲哚衍生物）在移植结局中具有免疫调节作用，但需要进一步研究以阐明与HCT后环境相关的机制。了解肠道微生物组与移植后结果之间的机制关系对于降低与移植相关的风险，告知预防性程序并确保无同种异体反应性的最佳免疫重建是必要的。在这里，我们总结了目前对细菌群落，它们的个体成员和它们在allo-HCT和稳态环境中产生的具有免疫功能的代谢物之间复杂关系的理解。
Allogenic hematopoietic stem-cell transplantation (allo-HCT) is a curative-intent immunotherapy for high-risk hematological malignancies and immune deficiencies. Allo-HCT carries a high risk of treatment-related mortality (TRM), largely due to infection or graft-versus-host disease (GVHD). Robust immune recovery is essential for optimal patient outcomes, given the immunologic graft-versus-leukemia effect prevents relapse, and functional innate and adaptive immunity are both needed for the prevention and control of infection. Most simply, we measure immune recovery by enumerating donor lymphocyte subsets in circulation. In functional terms, ideal immune recovery is more difficult to define, and current lab techniques are limited to the measurement of specific vaccine-responses or mitogens ex vivo. Clinically, poor immune function manifests as problematic infection with viral, bacterial and fungal organisms. Furthermore, the ideal recovering immune system is capable of exerting graft-versus-tumor effects to prevent relapse, and does not induce graft-versus-host disease. Large clinical observational studies have linked loss of diversity within the gut microbiome with adverse transplant outcomes including decreased overall survival and increased acute and chronic GVHD. Furthermore, the correlation between intestinal microbial communities and numeric lymphocyte recovery has now been reported using a number of approaches. Large sets of clinically available white blood cell count data, clinical flow cytometry of lymphocyte subsets and bespoke flow cytometry analyses designed to capture microbiota-specific T cells (e.g. Mucosal-associated invariant T cells, subsets of the gd T cells) have all been leveraged in an attempt to understand links between the microbiota and the recovering immune system in HCT patients. Additionally, preclinical studies suggest an immunomodulatory role for bacterial metabolites (including butyrate, secondary bile acids, and indole derivatives from tryptophan metabolism) in transplant outcomes, though further studies are needed to unravel mechanisms relevant to the post-HCT setting. An understanding of mechanistic relationships between the intestinal microbiome and post-transplant outcomes is necessary for reduction of risk associated with transplant, to inform prophylactic procedures, and ensure optimal immune reconstitution without alloreactivity. Here, we summarize the current understanding of the complex relationship between bacterial communities, their individual members, and the metabolites they produce with immune function in both the allo-HCT and steady-state setting.
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影响因子：
17.1
作者：
通讯作者：
--
影响因子：
82.9
作者：
Benakis C;Brea D;Caballero S;Faraco G;Moore J;Murphy M;Sita G;Racchumi G;Ling L;Pamer EG;Iadecola C;Anrather J
通讯作者：
Anrather J
影响因子：
29
作者：
Donohoe DR;Garge N;Zhang X;Sun W;O'Connell TM;Bunger MK;Bultman SJ
通讯作者：
Bultman SJ
DOI：
10.1126/science.aax6624
发表时间：
2019-10-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Constantinides MG;Link VM;Tamoutounour S;Wong AC;Perez-Chaparro PJ;Han SJ;Chen YE;Li K;Farhat S;Weckel A;Krishnamurthy SR;Vujkovic-Cvijin I;Linehan JL;Bouladoux N;Merrill ED;Roy S;Cua DJ;Adams EJ;Bhandoola A;Scharschmidt TC;Aubé J;Fischbach MA;Belkaid Y
通讯作者：
Belkaid Y
影响因子：
4.7
作者：
Andrlová H;van den Brink MRM;Markey KA
通讯作者：
Markey KA