Hematopoietic Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
The Michener Institute of Education at University Health Network, Toronto, Canada.
J Cell Physiol. 2020 Dec;235(12):9080-9097. doi: 10.1002/jcp.29769. Epub 2020 May 7.
Hematologic malignancies comprise a considerable part of cancers with high mortality at any age. Since the introduction of hematopoietic stem cell transplantation (HSCT), the overall survival of patients dramatically increased. The main goal of HSCT is the induction of a graft-versus-leukemia effect to eradicate the residual cancer cells and also reconstitute a healthy immune system for patients. However, relapse is a nettlesome challenge of HSCT. Like many other tumors, hematologic cancer cells induce immune exhaustion leading to immune escape and relapses after HSCT. Besides malignant cells, inhibitory cells such as tumor-associated macrophages and myeloid-derived suppressor cells express various inhibitory receptors capable of inducing exhaustion in immune cells, especially T and natural killer cells. The significance of immune checkpoint blocking in tumor regression in clinical trials led to the 2018 Nobel Prize in Physiology/Medicine. Here, we reviewed the clinical roles of immune checkpoints in hematologic malignancies and post-HSCT relapses.
血液系统恶性肿瘤是一种高死亡率的癌症，在任何年龄段都有相当大的比例。自造血干细胞移植（HSCT）引入以来，患者的总生存率显著提高。HSCT 的主要目的是诱导移植物抗白血病效应，以根除残留的癌细胞，并为患者重建健康的免疫系统。然而，复发是 HSCT 的一个棘手挑战。与许多其他肿瘤一样，血液系统癌细胞诱导免疫衰竭，导致免疫逃逸和 HSCT 后复发。除了恶性细胞外，抑制性细胞如肿瘤相关巨噬细胞和髓系来源的抑制性细胞表达各种抑制性受体，能够诱导免疫细胞，特别是 T 细胞和自然杀伤细胞衰竭。免疫检查点阻断在临床试验中对肿瘤消退的重要性导致了 2018 年诺贝尔生理学或医学奖。在这里，我们回顾了免疫检查点在血液系统恶性肿瘤和 HSCT 后复发中的临床作用。
