Departments of Stem Cell Transplantation and Cellular Therapy (G.A., E.A.M.), Leukemia (N.D.), and Breast Surgical (E.A.M.) Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Departments of Stem Cell Transplantation and Cellular Therapy (G.A., E.A.M.), Leukemia (N.D.), and Breast Surgical (E.A.M.) Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Pharmacol Rev. 2016 Oct;68(4):1014-1025. doi: 10.1124/pr.116.012682.
The use of antibodies that target immune checkpoint molecules on the surface of T-lymphocytes and/or tumor cells has revolutionized our approach to cancer therapy. Cytotoxic-T-lymphocyte antigen (CTLA-4) and programmed cell death protein 1 (PD-1) are the two most commonly targeted immune checkpoint molecules. Although the role of antibodies that target CTLA-4 and PD-1 has been established in solid tumor malignancies and Food and Drug Administration approved for melanoma and non-small cell lung cancer, there remains a desperate need to incorporate immune checkpoint inhibition in hematologic malignancies. Unlike solid tumors, a number of considerations must be addressed to appropriately employ immune checkpoint inhibition in hematologic malignancies. For example, hematologic malignancies frequently obliterate the bone marrow and lymph nodes, which are critical immune organs that must be restored for appropriate response to immune checkpoint inhibition. On the other hand, hematologic malignancies are the quintessential immune responsive tumor type, as proven by the success of allogeneic stem cell transplantation (allo-SCT) in hematologic malignancies. Also, sharing an immune cell lineage, malignant hematologic cells often express immune checkpoint molecules that are absent in solid tumor cells, thereby offering direct targets for immune checkpoint inhibition. A number of clinical trials have demonstrated the potential for immune checkpoint inhibition in hematologic malignancies before and after allo-SCT. The ongoing clinical studies and complimentary immune correlatives are providing a growing body of knowledge regarding the role of immune checkpoint inhibition in hematologic malignancies, which will likely become part of the standard of care for hematologic malignancies.
靶向 T 淋巴细胞和/或肿瘤细胞表面免疫检查点分子的抗体的使用彻底改变了我们的癌症治疗方法。细胞毒性 T 淋巴细胞抗原 (CTLA-4) 和程序性细胞死亡蛋白 1 (PD-1) 是两种最常被靶向的免疫检查点分子。尽管靶向 CTLA-4 和 PD-1 的抗体在实体瘤恶性肿瘤中的作用已得到确立，并且已被食品和药物管理局批准用于黑色素瘤和非小细胞肺癌，但仍迫切需要将免疫检查点抑制纳入血液恶性肿瘤。与实体瘤不同，必须解决许多问题才能在血液恶性肿瘤中适当使用免疫检查点抑制。例如，血液恶性肿瘤经常破坏骨髓和淋巴结，这些是对免疫检查点抑制有适当反应所必需的关键免疫器官。另一方面，血液恶性肿瘤是典型的免疫反应性肿瘤类型，正如异基因干细胞移植 (allo-SCT) 在血液恶性肿瘤中的成功所证明的那样。此外，恶性血液细胞具有共同的免疫细胞谱系，经常表达在实体瘤细胞中不存在的免疫检查点分子，从而为免疫检查点抑制提供了直接靶点。许多临床试验已经证明了免疫检查点抑制在 allo-SCT 前后的血液恶性肿瘤中的潜力。正在进行的临床研究和补充免疫相关性研究为免疫检查点抑制在血液恶性肿瘤中的作用提供了越来越多的知识，这可能成为血液恶性肿瘤标准治疗的一部分。
