Antitumor immunity and cancer stem cells.
Antitumor immunity and cancer stem cells.
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DOI：
10.1111/j.1749-6632.2009.04568.x
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发表时间：
2009-09
影响因子：
5.2
通讯作者：
Frank MH
中科院分区：
文献类型：
--
作者：
Schatton T;Frank MH
能够产生更分化的肿瘤细胞后代的自我更新癌症干细胞（CSC）是白血病和几种实体癌的肿瘤发生和肿瘤进展所必需的。CSC引起肿瘤发生和生长的机制目前尚不清楚。最近的研究结果表明，宿主免疫能力和癌症发展率之间的负相关性，提出了只有少数有限的恶性细胞，即CSC，可能具有逃避宿主抗肿瘤免疫的表型和功能特征的可能性。在人类恶性黑色素瘤，一种高度免疫原性的癌症，我们最近确定了恶性黑色素瘤起始细胞（MMIC），一种新型的CSC，基于选择性表达的化疗耐药性介导ABCB 5。在这里，我们提出了ABCB 5 + MMIC的相对免疫豁免的证据，表明目前的免疫治疗策略的难治性。我们讨论了我们的研究结果的背景下建立的生理干细胞的免疫调节功能，并在负责任的机制下调对肿瘤的免疫反应。我们认为MMIC亚群可能是黑色素瘤免疫逃避的原因，免疫调节可能是CSC促进肿瘤生长和免疫治疗抵抗的一种机制。因此，MMIC驱动的肿瘤逃避免疫介导的排斥反应的可能性对当前的黑色素瘤免疫治疗具有重要意义。
Self-renewing cancer stem cells (CSC) capable of spawning more differentiated tumor cell progeny are required for tumorigenesis and neoplastic progression of leukemias and several solid cancers. The mechanisms by which CSC cause tumor initiation and growth are currently unknown. Recent findings that suggest a negative correlation between degrees of host immunocompetence and rates of cancer development raise the possibility that only a restricted minority of malignant cells, namely CSC, may possess the phenotypic and functional characteristics to evade host antitumor immunity. In human malignant melanoma, a highly immunogenic cancer, we recently identified malignant melanoma initiating cells (MMIC), a novel type of CSC, based on selective expression of the chemoresistance mediator ABCB5. Here we present evidence of a relative immune privilege of ABCB5+ MMIC, suggesting refractoriness to current immunotherapeutic treatment strategies. We discuss our findings in the context of established immunomodulatory functions of physiologic stem cells and in relation to mechanisms responsible for the downregulation of immune responses against tumors. We propose that the MMIC subset might be responsible for melanoma immune evasion and that immunomodulation might represent one mechanism by which CSC advance tumorigenic growth and resistance to immunotherapy. Accordingly, the possibility of an MMIC-driven tumor escape from immune-mediated rejection has important implications for current melanoma immunotherapy.
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影响因子：
5.2
作者：
Chang, Chun-Jung;Yen, Men-Luh;Yen, B. Linju
通讯作者：
Yen, B. Linju
影响因子：
5.8
作者：
Cabrera, Teresa;Lara, Ester;Garrido, Federico
通讯作者：
Garrido, Federico
DOI：
10.1073/pnas.0703478104
发表时间：
2007-06-12
影响因子：
11.1
作者：
Dalerba, Piero;Dylla, Scott J.;Clarke, Michael F.
通讯作者：
Clarke, Michael F.
影响因子：
20.3
作者：
Aggarwal, S;Pittenger, MF
通讯作者：
Pittenger, MF
影响因子：
20.3
作者：
Beyth, S;Borovsky, Z;Rachmilewitz, J
通讯作者：
Rachmilewitz, J