胶质母细胞瘤的免疫治疗:肿瘤模型开发中的当前策略和挑战。

Immunotherapy of Glioblastoma: Current Strategies and Challenges in Tumor Model Development.

机构信息

Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, 111 Večna pot, SI-1000 Ljubljana, Slovenia.

International Postgraduate School Jozef Stefan, 39 Jamova ulica, SI-1000 Ljubljana, Slovenia.

出版信息

Cells. 2021 Jan 29;10(2):265. doi: 10.3390/cells10020265.

Abstract

Glioblastoma is the most common brain malignant tumor in the adult population, and immunotherapy is playing an increasingly central role in the treatment of many cancers. Nevertheless, the search for effective immunotherapeutic approaches for glioblastoma patients continues. The goal of immunotherapy is to promote tumor eradication, boost the patient's innate and adaptive immune responses, and overcome tumor immune resistance. A range of new, promising immunotherapeutic strategies has been applied for glioblastoma, including vaccines, oncolytic viruses, immune checkpoint inhibitors, and adoptive cell transfer. However, the main challenges of immunotherapy for glioblastoma are the intracranial location and heterogeneity of the tumor as well as the unique, immunosuppressive tumor microenvironment. Owing to the lack of appropriate tumor models, there are discrepancies in the efficiency of various immunotherapeutic strategies between preclinical studies (with in vitro and animal models) on the one hand and clinical studies (on humans) on the other hand. In this review, we summarize the glioblastoma characteristics that drive tolerance to immunotherapy, the currently used immunotherapeutic approaches against glioblastoma, and the most suitable tumor models to mimic conditions in glioblastoma patients. These models are improving and can more precisely predict patients' responses to immunotherapeutic treatments, either alone or in combination with standard treatment.

摘要

胶质母细胞瘤是成人中最常见的脑恶性肿瘤,免疫疗法在许多癌症的治疗中发挥着越来越核心的作用。然而,寻找有效的胶质母细胞瘤患者免疫治疗方法仍在继续。免疫疗法的目标是促进肿瘤的消除,增强患者的先天和适应性免疫反应,并克服肿瘤的免疫抵抗。一系列新的、有前途的免疫治疗策略已被应用于胶质母细胞瘤,包括疫苗、溶瘤病毒、免疫检查点抑制剂和过继细胞转移。然而,胶质母细胞瘤免疫治疗的主要挑战是肿瘤的颅内位置和异质性以及独特的、免疫抑制性肿瘤微环境。由于缺乏合适的肿瘤模型,一方面是临床前研究(体外和动物模型),另一方面是临床研究(针对人类),各种免疫治疗策略的效率存在差异。在这篇综述中,我们总结了导致对免疫疗法产生耐受性的胶质母细胞瘤特征、目前用于胶质母细胞瘤的免疫治疗方法以及最适合模拟胶质母细胞瘤患者情况的肿瘤模型。这些模型正在不断改进,可以更准确地预测患者对免疫治疗的反应,无论是单独使用还是与标准治疗联合使用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7a9/7912469/0f05c3849530/cells-10-00265-g001.jpg

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