Hematology and Clinical Immunology and Bone Marrow Transplant Program, Department of Medicine, University of Perugia, Perugia, Italy.
Front Immunol. 2019 Dec 17;10:2901. doi: 10.3389/fimmu.2019.02901. eCollection 2019.
Since their discovery CD4FOXP3 regulatory T cells (Tregs) represented a promising tool to induce tolerance in allogeneic hematopoietic cell transplantation. Preclinical models proved that adoptive transfer of Tregs or the use of compounds that can favor their function are effective for prevention and treatment of graft-vs.-host disease (GvHD). Following these findings, Treg-based therapies have been employed in clinical trials. Adoptive immunotherapy with Tregs effectively prevents GvHD induced by alloreactive T cells in the setting of one HLA haplotype mismatched hematopoietic transplantation. The absence of post transplant pharmacologic immunosuppression unleashes T-cell mediated graft-vs.-tumor (GvT) effect, which results in an unprecedented, almost complete control of leukemia relapse in this setting. In the present review, we will report preclinical studies and clinical trials that demonstrate Treg ability to promote donor engraftment, protect from GvHD and improve GvT effect. We will also discuss new strategies to further enhance efficacy of Treg-based therapies.
自发现 CD4FOXP3 调节性 T 细胞（Tregs）以来，它们代表了一种在异基因造血细胞移植中诱导耐受的有前途的工具。临床前模型证明，Tregs 的过继转移或使用可以促进其功能的化合物对于预防和治疗移植物抗宿主病（GvHD）是有效的。基于这些发现，Treg 为基础的治疗方法已在临床试验中应用。在 HLA 单倍型错配造血移植的背景下，Tregs 的过继免疫疗法可有效预防同种反应性 T 细胞引起的 GvHD。移植后没有药物免疫抑制作用，释放了 T 细胞介导的移植物抗肿瘤（GvT）效应，导致在这种情况下白血病复发得到前所未有的、几乎完全控制。在本综述中，我们将报告临床前研究和临床试验，证明 Treg 能够促进供体植入、预防 GvHD 和改善 GvT 效应。我们还将讨论进一步增强 Treg 为基础的治疗方法疗效的新策略。
