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用于评估结直肠癌免疫反应和肿瘤微生物组相互作用的肿瘤模型。

Tumor models to assess immune response and tumor-microbiome interactions in colorectal cancer.

机构信息

Department of Surgery, University of Minnesota, Minneapolis, MN 55455, United States of America.

Department of Surgery, University of Minnesota, Minneapolis, MN 55455, United States of America; Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, United States of America.

出版信息

Pharmacol Ther. 2022 Mar;231:107981. doi: 10.1016/j.pharmthera.2021.107981. Epub 2021 Sep 2.

Abstract

Despite significant advances over the past 2 decades in preventive screening and therapy aimed at improving patient survival, colorectal cancer (CRC) remains the second most common cause of cancer death in the United States. The average 5-year survival rate of CRC patients with positive regional lymph nodes is only 40%, while less than 5% of patients with distant metastases survive beyond 5 years. There is a critical need to develop novel therapies that can improve overall survival in patients with poor prognoses, particularly since 60% of them are diagnosed at an advanced stage. Pertinently, immune checkpoint blockade therapy has dramatically changed how we treat CRC patients with microsatellite-instable high tumors. Furthermore, accumulating evidence shows that changes in gut microbiota are associated with the regulation of host antitumor immune response and cancer progression. Appropriate animal models are essential to deciphering the complex mechanisms of host antitumor immune response and tumor-gut microbiome metabolic interactions. Here, we discuss various mouse models of colorectal cancer that are developed to address key questions on tumor immune response and tumor-microbiota interactions. These CRC models will also serve as resourceful tools for effective preclinical studies.

摘要

尽管在过去的 20 年中,针对提高患者生存率的预防筛查和治疗取得了重大进展,但结直肠癌 (CRC) 仍然是美国癌症死亡的第二大主要原因。区域淋巴结阳性的 CRC 患者的 5 年平均生存率仅为 40%,而远处转移患者的生存率不足 5%。因此,迫切需要开发新的治疗方法,以改善预后不良患者的总体生存率,特别是因为其中 60%的患者被诊断为晚期。相关的是,免疫检查点阻断疗法极大地改变了我们治疗微卫星不稳定高肿瘤的 CRC 患者的方式。此外,越来越多的证据表明,肠道微生物群的变化与宿主抗肿瘤免疫反应和癌症进展的调节有关。适当的动物模型对于解析宿主抗肿瘤免疫反应和肿瘤-肠道微生物群代谢相互作用的复杂机制至关重要。在这里,我们讨论了为解决肿瘤免疫反应和肿瘤-微生物群相互作用方面的关键问题而开发的各种结直肠癌小鼠模型。这些 CRC 模型也将成为有效的临床前研究的有价值工具。

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