摘要
背景:多发性骨髓瘤(MM)细胞通过T细胞功能缺陷,无效抗原呈递而抑制有效的抗MM免疫应答的发展;吞噬能力降低;自然杀伤和树突状细胞功能障碍;降低对IL-2的反应性和B细胞免疫缺陷;上调抑制途径;并产生过量的促炎细胞因子。此外,包括浆细胞样树突状细胞和巨噬细胞的免疫细胞触发肿瘤细胞增殖,存活和耐药性。在MM患者中免疫治疗的有用性首先通过在同种异体骨髓(BM)移植的背景下鉴定移植物对骨髓瘤的作用而得到支持。随后,将沙利度胺及其衍生物,免疫调节药物(IMiD)以及(免疫)蛋白酶体抑制剂纳入MM方案中显着改善了MM患者在过去15年中的结果。尽管有这些前所未有的治疗进展,MM仍然是不治之症。 目的:本文回顾了新型免疫治疗方法,旨在恢复MM BM微环境免疫学位置的平衡。 方法:对主要文章以及会议摘要(例如美国血液学协会,美国临床肿瘤学会,美国癌症协会,美国肿瘤学会,美国癌症协会研究,欧洲血液学协会和多发性骨髓瘤研讨会),实践指南和临床试验登记。 结果:将单克隆抗体,免疫检查点抑制剂,嵌合抗原受体工程(CAR)T细胞,遗传工程化T细胞和疫苗接种,特别是树突状细胞的癌症疫苗纳入现有方案中可能显着改善MM患者的结果不久的将来。 结论:由于持续努力,针对骨髓微环境中的免疫细菌,我们相信MM的免疫治疗的兴起将在未来十年内引起许多患者的长期回应。
关键词: 多发性骨髓瘤,免疫微环境,干细胞移植,免疫调节药物(IMiDs),基于抗体和肽的策略,过继疗法,CAR细胞,TCR工程T细胞,免疫检查点封闭,BiTE®,疫苗。
图形摘要
Current Cancer Drug Targets
Title:Targeting the Immune Niche within the Bone Marrow Microenvironment: The Rise of Immunotherapy in Multiple Myeloma
Volume: 17 Issue: 9
关键词: 多发性骨髓瘤,免疫微环境,干细胞移植,免疫调节药物(IMiDs),基于抗体和肽的策略,过继疗法,CAR细胞,TCR工程T细胞,免疫检查点封闭,BiTE®,疫苗。
摘要: Background: Multiple Myeloma (MM) cells inhibit the development of an effective anti- MM immune response via defects in T cell function, ineffective antigen presentation; reduced phagocytic capacity; natural killer and dendritic cell dysfunction; decreased responsiveness to IL-2 and defects in B cell immunity; upregulation of inhibitory pathways; and production of excessive proinflammatory cytokines. Moreover, immune cells including plasmacytoid dendritic cells and macrophages trigger tumor cell proliferation, survival, and drug resistance. The usefulness of immunotherapies in MM patients has first been supported by the identification of the graft-versus-myeloma effect in the context of allogeneic bone marrow (BM) transplantation. Subsequently, the inclusion of thalidomide and its derivatives, the Immunomodulatory Drugs (IMiDs) as well as of (immuno) proteasome inhibitors into MM regimens dramatically improved MM patients outcome during the last 15 years. Despite these unprecedented therapeutic advances MM remains an incurable disease.
Objective: This article reviews novel immunotherapeutic approaches, which aim to restore the balance within the immunologic niche of the MM BM microenvironment.
Method: A systematic search was conducted of the Pubmed Medline, Embase, and Cochrane Library databases for primary articles, as well as of conference abstracts (e.g., of the American Society of Hematology, the American Society of Clinical Oncology, the American Association of Cancer Research, the European Hematology Association, and the Multiple Myeloma Workshop), practice guidelines, and registries of clinical trials.
Results: The inclusion of monoclonal antibodies, immune checkpoint inhibitors, chimeric antigen receptor-engineered (CAR) T cells, genetically engineered T cells, and vaccination, dendritic cellbased cancer vaccines in particular, into existing regimens is likely to significantly improve MM patient outcome in the near future.
Conclusion: Given continuing efforts to target the immune niche within the bone marrow microenvironment we are confident that the rise of immunotherapies in MM will result in long-lasting responses in many of our patients within the next decade.
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Cite this article as:
Targeting the Immune Niche within the Bone Marrow Microenvironment: The Rise of Immunotherapy in Multiple Myeloma, Current Cancer Drug Targets 2017; 17 (9) . https://dx.doi.org/10.2174/1568009617666170214103834
DOI https://dx.doi.org/10.2174/1568009617666170214103834 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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