Using the canine microbiome to bridge translation of cancer immunotherapy from pre-clinical murine models to human clinical trials.
Using the canine microbiome to bridge translation of cancer immunotherapy from pre-clinical murine models to human clinical trials.
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DOI：
10.3389/fimmu.2022.983344
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
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微生物组显然已被确立为肿瘤免疫学和免疫治疗的前沿领域。越来越多的证据支持微生物组在免疫监视、自我耐受以及对免疫检查点抑制剂（例如抗 PD-L1 和 CTLA-4 阻断）的反应中的作用。此外，最近的研究，包括使用粪便微生物移植（FMT）的研究表明，对检查点免疫疗法的反应可以通过肠道微生物组调节来赋予或消除。因此，评估微生物群与宿主免疫和代谢相互作用的研究仍然是一个具有高影响力的研究领域。虽然小鼠模型中的观察结果强调了微生物组对治疗反应的重要性，但我们对这些相互作用背后的确切机制缺乏足够的了解。此外，小鼠和人类肠道微生物组的组成可能非常不同，无法发现所有相关的肠道微生物生物标志物。狗身上的多种癌症，包括淋巴瘤、高级神经胶质瘤、黑色素瘤和骨肉瘤（OSA），与人类的类似癌症非常相似，特别是在转移、疾病复发和治疗反应方面。重要的是，患有这些自发性癌症的狗也具有完整的免疫系统，这表明这些受试者的微生物组分析可以提供高产信息，特别是在目前在犬类比较肿瘤学中迅速扩展的新型免疫治疗方案的背景下。此外，随着肿瘤微生物疗法的开发是为了改变肠道微生物组以获得最大反应性，具有完整免疫系统的大型动物模型将有助于试验干预措施和监测不良事件。临床前机制研究和大型动物试验共同有助于充分释放微生物组作为癌症诊断和治疗靶点的潜力。
The microbiome has clearly been established as a cutting-edge field in tumor immunology and immunotherapy. Growing evidence supports the role of the microbiome in immune surveillance, self-tolerance, and response to immune checkpoint inhibitors such as anti PD-L1 and CTLA-4 blockade. Moreover, recent studies including those using fecal microbial transplantation (FMT) have demonstrated that response to checkpoint immunotherapies may be conferred or eliminated through gut microbiome modulation. Consequently, studies evaluating microbiota-host immune and metabolic interactions remain an area of high impact research. While observations in murine models have highlighted the importance of the microbiome in response to therapy, we lack sufficient understanding of the exact mechanisms underlying these interactions. Furthermore, mouse and human gut microbiome composition may be too dissimilar for discovery of all relevant gut microbial biomarkers. Multiple cancers in dogs, including lymphoma, high grade gliomas, melanomas and osteosarcoma (OSA) closely resemble their human analogues, particularly in regard to metastasis, disease recurrence and response to treatment. Importantly, dogs with these spontaneous cancers also have intact immune systems, suggesting that microbiome analyses in these subjects may provide high yield information, especially in the setting of novel immunotherapy regimens which are currently expanding rapidly in canine comparative oncology. Additionally, as onco-microbiotic therapies are developed to modify gut microbiomes for maximal responsiveness, large animal models with intact immune systems will be useful for trialing interventions and monitoring adverse events. Together, pre-clinical mechanistic studies and large animal trials can help fully unlock the potential of the microbiome as a diagnostic and therapeutic target in cancer.
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影响因子：
30.3
作者：
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通讯作者：
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影响因子：
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