Utilizing cell-based therapeutics to overcome immune evasion in hematologic malignancies.
Utilizing cell-based therapeutics to overcome immune evasion in hematologic malignancies.
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DOI：
10.1182/blood-2015-12-629089
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发表时间：
2016-06
期刊：
影响因子：
20.3
通讯作者：
Chuang Sun;G. Dotti;B. Savoldo
中科院分区：
文献类型：
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作者：
Chuang Sun;G. Dotti;B. Savoldo
血液恶性肿瘤为基于细胞的免疫疗法提供了合适的测试环境，这种疗法是由同种异体造血干细胞移植的发展所开创的。所有类型的基于细胞的疗法，从供体淋巴细胞输注到树突状细胞疫苗，以及肿瘤特异性细胞毒性T细胞和自然杀伤细胞的过继转移，都已在临床上转化为血液恶性肿瘤。最近嵌合抗原受体修饰的 T 淋巴细胞在 B 细胞恶性肿瘤中的成功刺激了这种方法在其他血液肿瘤中的发展。同样，检查点抑制剂作为单一药物的显着活性激发了人们对与其他基于细胞的免疫疗法的潜在组合的热情。然而，肿瘤细胞不断发展出各种策略来逃避免疫介导的消除。同时，免疫抑制细胞的募集和抑制因子的释放有助于肿瘤微环境的发展，从而阻碍有效免疫反应的启动或阻断免疫效应细胞的功能。了解肿瘤细胞如何逃避免疫攻击并有利于免疫抑制对于改进基于免疫细胞的疗法和开发合理的组合方法至关重要。
Hematologic malignancies provide a suitable testing environment for cell-based immunotherapies, which were pioneered by the development of allogeneic hematopoietic stem cell transplant. All types of cell-based therapies, from donor lymphocyte infusion to dendritic cell vaccines, and adoptive transfer of tumor-specific cytotoxic T cells and natural killer cells, have been clinically translated for hematologic malignancies. The recent success of chimeric antigen receptor-modified T lymphocytes in B-cell malignancies has stimulated the development of this approach toward other hematologic tumors. Similarly, the remarkable activity of checkpoint inhibitors as single agents has created enthusiasm for potential combinations with other cell-based immune therapies. However, tumor cells continuously develop various strategies to evade their immune-mediated elimination. Meanwhile, the recruitment of immunosuppressive cells and the release of inhibitory factors contribute to the development of a tumor microenvironment that hampers the initiation of effective immune responses or blocks the functions of immune effector cells. Understanding how tumor cells escape from immune attack and favor immunosuppression is essential for the improvement of immune cell-based therapies and the development of rational combination approaches.