Retention of Donor T Cells in Lymphohematopoietic Tissue and Augmentation of Tissue PD-L1 Protection for Prevention of GVHD While Preserving GVL Activity.
Retention of Donor T Cells in Lymphohematopoietic Tissue and Augmentation of Tissue PD-L1 Protection for Prevention of GVHD While Preserving GVL Activity.
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DOI：
10.3389/fimmu.2022.907673
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发表时间：
2022
影响因子：
7.3
通讯作者：
Zeng, Defu
中科院分区：
文献类型：
--
作者：
Song, Qingxiao;Nasri, Ubaydah;Nakamura, Ryotaro;Martin, Paul J.;Zeng, Defu
关键词：
异基因造血细胞移植（Allo - HCT）是血液系统恶性肿瘤（如白血病和淋巴瘤）的一种根治性疗法，这得益于同种异体反应性T细胞介导的移植物抗白血病（GVL）效应，该效应能够清除残留的恶性细胞并预防复发。然而，同样的同种异体反应性T细胞会引发一种严重的副作用，即移植物抗宿主病（GVHD）。GVHD和GVL发生在不同的器官和组织中，GVHD发生在靶器官（如肠道、肝脏、肺、皮肤等），而GVL发生在淋巴造血组织，这里也是血液癌细胞主要存在的部位。目前用于治疗GVHD的免疫抑制药物会抑制供体T细胞的活化和扩增，导致GVHD和GVL活性均降低，进而增加癌症复发风险。为预防GVHD，重要的是要让同种异体反应性T细胞在淋巴造血组织中充分活化和扩增，同时阻止供体T细胞迁移至GVHD靶组织，并通过诸如程序性死亡配体1（PD - L1）与程序性死亡受体1（PD - 1）相互作用等保护机制，使浸润到靶组织的T细胞产生免疫耐受。在这篇综述中，我们将总结防止供体T细胞迁移至GVHD靶组织的主要方法，以及在维持淋巴造血组织中强大GVL活性的同时，增强GVHD靶组织中浸润T细胞免疫耐受的方法。
Allogeneic hematopoietic cell transplantation (Allo-HCT) is a curative therapy for hematological malignancies (i.e., leukemia and lymphoma) due to the graft-versus-leukemia (GVL) activity mediated by alloreactive T cells that can eliminate residual malignant cells and prevent relapse. However, the same alloreactive T cells can cause a serious side effect, known as graft-versus-host disease (GVHD). GVHD and GVL occur in distinct organ and tissues, with GVHD occurring in target organs (e.g., the gut, liver, lung, skin, etc.) and GVL in lympho-hematopoietic tissues where hematological cancer cells primarily reside. Currently used immunosuppressive drugs for the treatment of GVHD inhibit donor T cell activation and expansion, resulting in a decrease in both GVHD and GVL activity that is associated with cancer relapse. To prevent GVHD, it is important to allow full activation and expansion of alloreactive T cells in the lympho-hematopoietic tissues, as well as prevent donor T cells from migrating into the GVHD target tissues, and tolerize infiltrating T cells via protective mechanisms, such as PD-L1 interacting with PD-1, in the target tissues. In this review, we will summarize major approaches that prevent donor T cell migration into GVHD target tissues and approaches that augment tolerization of the infiltrating T cells in the GVHD target tissues while preserving strong GVL activity in the lympho-hematopoietic tissues.
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影响因子：
20.3
作者：
Bleakley, Marie;Otterud, Brith E.;Riddell, Stanley R.
通讯作者：
Riddell, Stanley R.
DOI：
10.1084/jem.20060376
发表时间：
2006-08-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.3
作者：
He, Wei;Racine, Jeremy J.;Johnston, Heather F.;Li, Xiaofan;Li, Nainong;Cassady, Kaniel;Liu, Can;Deng, Ruishu;Martin, Paul;Forman, Stephen;Zeng, Defu
通讯作者：
Zeng, Defu
影响因子：
20.3
作者：
Anderson, Britt E.;Taylor, Patricia A.;Shlomchik, Mark J.
通讯作者：
Shlomchik, Mark J.
影响因子：
4.3
作者：
Choi, Sung W.;Stiff, Patrick;Cooke, Kenneth;Ferrara, James L. M.;Braun, Thomas;Kitko, Carrie;Reddy, Pavan;Yanik, Gregory;Mineishi, Shin;Paczesny, Sophie;Hanauer, David;Pawarode, Attaphol;Peres, Edward;Rodriguez, Tulio;Smith, Scott;Levine, John E.
通讯作者：
Levine, John E.