Cancer Immunotherapy Getting Brainy: Visualizing the Distinctive CNS Metastatic Niche to Illuminate Therapeutic Resistance.
Cancer Immunotherapy Getting Brainy: Visualizing the Distinctive CNS Metastatic Niche to Illuminate Therapeutic Resistance.
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DOI：
10.1016/j.drup.2017.10.001
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发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
Smith BR
中科院分区：
文献类型：
--
作者：
Owyong M;Hosseini-Nassab N;Efe G;Honkala A;van den Bijgaart RJE;Plaks V;Smith BR
癌症免疫疗法（CIT）的出现及其在治疗原发性和转移性癌症方面的成功可能会大大改善患者的预后。尽管最近取得了进展，但许多恶性肿瘤仍然对CIT具有抗性，其中包括脑转移瘤，这是一种没有明显治愈的特别致命的疾病。脑的免疫学独特的生态位在免疫肿瘤学中引发了引人注目的新问题，例如免疫应答中组织特异性差异的影响，原发性肿瘤和远处转移瘤之间的异质性，以及时空动态在形成有效的抗肿瘤免疫应答中的作用。目前检查脑转移瘤免疫生物学的方法受到组织处理方法的限制，这些方法限制了空间数据收集，忽略了动态信息，并且不能概括肿瘤微环境的异质性。在目前的审查中，我们描述了如何高分辨率，实时成像工具，特别是活体显微镜（IVM），有助于回答这些问题。临床前癌症模型的IVM使关键免疫生物学和转移性生长现象的短期和长期观察成为可能，从而对脑转移的时空动力学、CIT与其中免疫元素的相互作用以及化疗和放疗的影响产生革命性的见解。我们描述了IVM研究小鼠脑转移瘤的效用，通过跟踪荧光标记细胞（包括癌细胞和免疫亚群）的迁移和生长，同时使用成像染料和其他信号产生机制监测光学窗口内的物理环境，以照亮转移灶内的血管生成、缺氧和/或CIT药物表达。我们的审查总结了目前的知识，脑转移瘤和免疫环境，介绍了CIT的现状和其在靶向脑转移瘤，以规避治疗耐药性的前景，并提出了途径，利用IVM研究CIT药物输送和治疗效果的临床前模型，最终将促进新药的发现和创新的联合治疗。
The advent of cancer immunotherapy (CIT) and its success in treating primary and metastatic cancer may offer substantially improved outcomes for patients. Despite recent advancements, many malignancies remain resistant to CIT, among which are brain metastases, a particularly virulent disease with no apparent cure. The immunologically unique niche of the brain has prompted compelling new questions in immuno-oncology such as the effects of tissue-specific differences in immune response, heterogeneity between primary tumors and distant metastases, and the role of spatiotemporal dynamics in shaping an effective anti-tumor immune response. Current methods to examine the immunobiology of metastases in the brain are constrained by tissue processing methods that limit spatial data collection, omit dynamic information, and cannot recapitulate the heterogeneity of the tumor microenvironment. In the current review, we describe how high-resolution, live imaging tools, particularly intravital microscopy (IVM), are instrumental in answering these questions. IVM of pre-clinical cancer models enables short- and long-term observations of critical immunobiology and metastatic growth phenomena to potentially generate revolutionary insights into the spatiotemporal dynamics of brain metastasis, interactions of CIT with immune elements therein, and influence of chemo- and radiotherapy. We describe the utility of IVM to study brain metastasis in mice by tracking the migration and growth of fluorescently-labeled cells, including cancer cells and immune subsets, while monitoring the physical environment within optical windows using imaging dyes and other signal generation mechanisms to illuminate angiogenesis, hypoxia, and/or CIT drug expression within the metastatic niche. Our review summarizes the current knowledge regarding brain metastases and the immune milieu, presents the current status of CIT and its prospects in targeting brain metastases to circumvent therapeutic resistance, and proposes avenues to utilize IVM to study CIT drug delivery and therapeutic efficacy in preclinical models that will ultimately facilitate novel drug discovery and innovative combination therapies.
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影响因子：
3.7
作者：
Belcaid Z;Phallen JA;Zeng J;See AP;Mathios D;Gottschalk C;Nicholas S;Kellett M;Ruzevick J;Jackson C;Albesiano E;Durham NM;Ye X;Tran PT;Tyler B;Wong JW;Brem H;Pardoll DM;Drake CG;Lim M
通讯作者：
Lim M
影响因子：
6.6
作者：
Chacko AM;Li C;Pryma DA;Brem S;Coukos G;Muzykantov V
通讯作者：
Muzykantov V
DOI：
10.1084/jem.20061890
发表时间：
2007-02-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Boissonnas A;Fetler L;Zeelenberg IS;Hugues S;Amigorena S
通讯作者：
Amigorena S
影响因子：
1.2
作者：
Abdulreda, Midhat H.;Caicedo, Alejandro;Berggren, Per-Olof
通讯作者：
Berggren, Per-Olof
影响因子：
82.9
作者：
Brown, EB;Campbell, RB;Jain, RK
通讯作者：
Jain, RK