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.

中文翻译：

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针对血液系统恶性肿瘤中的免疫检查点。


使用针对 T 淋巴细胞和/或肿瘤细胞表面免疫检查点分子的抗体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) 是两种最常见的靶向免疫检查点分子。尽管针对 CTLA-4 和 PD-1 的抗体在实体瘤恶性肿瘤中的作用已得到证实，并且美国食品和药物管理局已批准用于黑色素瘤和非小细胞肺癌，但仍然迫切需要将免疫检查点抑制纳入血液恶性肿瘤中。与实体瘤不同，必须考虑许多因素才能在血液恶性肿瘤中适当采用免疫检查点抑制。例如，血液恶性肿瘤经常会消灭骨髓和淋巴结，而它们是至关重要的免疫器官，必须恢复它们才能对免疫检查点抑制做出适当的反应。另一方面，同种异体干细胞移植（allo-SCT）在血液恶性肿瘤中的成功证明了血液恶性肿瘤是典型的免疫反应性肿瘤类型。此外，由于共享免疫细胞谱系，恶性血液细胞通常表达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直接靶标。大量临床试验已经证明了异基因 SCT 前后免疫检查点抑制在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正在提供越来越多关于免疫检查点抑制在血液恶性肿瘤中的作用的知识，这可能会成为血液恶性肿瘤护理标准的一部分。