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迈向使用多重免疫组织化学和计算机模拟方法来定义肿瘤免疫微环境的精准免疫疗法。

Toward precision immunotherapy using multiplex immunohistochemistry and in silico methods to define the tumor immune microenvironment.

作者信息

Widodo Samuel S, Hutchinson Ryan A, Fang Yitong, Mangiola Stefano, Neeson Paul J, Darcy Phillip K, Barrow Alexander D, Hovens Christopher M, Dinevska Marija, Stylli Stanley S, Mantamadiotis Theo

机构信息

Department of Microbiology and Immunology, The University of Melbourne, Melbourne, Australia.

Department of Clinical Pathology, The University of Melbourne, Melbourne, Australia.

出版信息

Cancer Immunol Immunother. 2021 Jul;70(7):1811-1820. doi: 10.1007/s00262-020-02801-7. Epub 2021 Jan 3.

Abstract

Recent developments in cancer immunotherapy promise better outcomes for cancer patients, although clinical trials for difficult to treat cancers such as malignant brain cancer present special challenges, showing little response to first generation immunotherapies. Reasons for differences in immunotherapy response in some cancer types are likely due to the nature of tumor microenvironment, which harbors multiple cell types which interact with tumor cells to establish immunosuppression. The cell types which appear to hold the key in regulating tumor immunosuppression are the tumor-infiltrating immune cells. The current standard treatment for difficult to treat cancer, including the most malignant brain cancer, glioblastoma, continues to offer a bleak outlook for patients. Immune-profiling and correlation with pathological and clinical data will lead to a deeper understanding of the tumor immune microenvironment and contribute toward the selection, optimization and development of novel precision immunotherapies. Here, we review the current understanding of the tumor microenvironmental landscape in glioblastoma with a focus on next-generation technologies including multiplex immunofluorescence and computational approaches to map the brain tumor microenvironment to decipher the role of the immune system in this lethal malignancy.

摘要

癌症免疫疗法的最新进展有望为癌症患者带来更好的治疗效果,尽管针对恶性脑癌等难治性癌症的临床试验面临特殊挑战,对第一代免疫疗法反应甚微。某些癌症类型中免疫疗法反应存在差异的原因可能在于肿瘤微环境的性质,该环境包含多种细胞类型,这些细胞与肿瘤细胞相互作用以建立免疫抑制。似乎在调节肿瘤免疫抑制中起关键作用的细胞类型是肿瘤浸润免疫细胞。包括最恶性的脑癌胶质母细胞瘤在内的难治性癌症的当前标准治疗方法,对患者而言前景依然黯淡。免疫分析以及与病理和临床数据的关联将有助于更深入地了解肿瘤免疫微环境,并有助于新型精准免疫疗法的选择、优化和开发。在此,我们综述了目前对胶质母细胞瘤肿瘤微环境格局的理解,重点关注包括多重免疫荧光和计算方法在内的下一代技术,以绘制脑肿瘤微环境图谱,从而解读免疫系统在这种致命恶性肿瘤中的作用。

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