Autologous Stem Cell Transplantation for Myeloma: Cytoreduction or an Immunotherapy?
Autologous Stem Cell Transplantation for Myeloma: Cytoreduction or an Immunotherapy?
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DOI：
10.3389/fimmu.2021.651288
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发表时间：
2021
影响因子：
7.3
通讯作者：
Hill GR
中科院分区：
文献类型：
--
作者：
Minnie SA;Hill GR
多发性骨髓瘤（MM）是一种骨髓（BM）原发性血液恶性肿瘤，其发病率在全球范围内不断增加。这种疾病的发病率和死亡率很高，而且基本上无法治愈。临床研究表明，自体干细胞移植（ASCT）在符合条件的患者中仍然有效，提供了超越单独新疗法的无进展生存期（PFS）获益。传统上，ASCT后PFS改善归因于清髓性化疗的细胞减少。然而，ASCT导致细胞减少以外的免疫效应，包括炎症、淋巴细胞耗竭、通过免疫原性细胞死亡引发T细胞和破坏肿瘤BM微环境。事实上，一小部分患者在ASCT后实现了非常长期的疾病控制，类似于在免疫介导的移植物vs.异基因SCT后骨髓瘤效应。这些临床观察结果加上最近在小鼠中的确定性研究表明，ASCT后的进展代表了T细胞耗竭导致的免疫逃逸，突出了新的免疫治疗维持策略预防ASCT巩固后骨髓瘤进展的潜力。
The incidence of multiple myeloma (MM), a bone marrow (BM) resident hematological malignancy, is increasing globally. The disease has substantial morbidity and mortality and remains largely incurable. Clinical studies show that autologous stem cell transplantation (ASCT) remains efficacious in eligible patients, providing a progression free survival (PFS) benefit beyond novel therapies alone. Conventionally, improved PFS after ASCT is attributed to cytoreduction from myeloablative chemotherapy. However, ASCT results in immune effects beyond cytoreduction, including inflammation, lymphodepletion, T cell priming via immunogenic cell death, and disruption of the tumor BM microenvironment. In fact, a small subset of patients achieve very long-term control of disease post-ASCT, akin to that seen in the context of immune-mediated graft-vs.-myeloma effects after allogeneic SCT. These clinical observations coupled with recent definitive studies in mice demonstrating that progression after ASCT represents immune escape as a consequence of T cell exhaustion, highlight the potential for new immunotherapy maintenance strategies to prevent myeloma progression following consolidation with ASCT.
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影响因子：
10.1
作者：
Chung DJ;Pronschinske KB;Shyer JA;Sharma S;Leung S;Curran SA;Lesokhin AM;Devlin SM;Giralt SA;Young JW
通讯作者：
Young JW
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
通过淋巴结消除来清除稳态细胞因子下沉，增强了采用转移的肿瘤特异性CD8+ T细胞的功效。
影响因子：
15.3
作者：
Gattinoni, Luca;Finkelstein, Steven E;Klebanoff, Christopher A;Antony, Paul A;Palmer, Douglas C;Spiess, Paul J;Hwang, Leroy N;Yu, Zhiya;Wrzesinski, Claudia;Heimann, David M;Surh, Charles D;Rosenberg, Steven A;Restifo, Nicholas P
通讯作者：
Restifo, Nicholas P
影响因子：
168.9
作者：
Cavo, Michele;Tacchetti, Paola;Baccarani, Michele
通讯作者：
Baccarani, Michele
影响因子：
20.3
作者：
Guillerey, Camille;Harjunpaeae, Heidi;Smyth, Mark J.
通讯作者：
Smyth, Mark J.