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多细胞肿瘤球体溶瘤病毒感染后细胞毒性淋巴细胞的产生与定量

Generation and Quantification of Cytotoxic Lymphocytes Following Oncolytic Virus Infection of Multi-cellular Tumor Spheroids.

作者信息

Jennings Victoria A, Ilkow Carolina S

机构信息

Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.

Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, Canada.

出版信息

Methods Mol Biol. 2023;2614:139-149. doi: 10.1007/978-1-0716-2914-7_10.

DOI:10.1007/978-1-0716-2914-7_10
PMID:36587124
Abstract

Oncolytic viruses (OVs) rapidly and specifically replicate in and kill tumor cells. OV-targeted infection of malignant cells has the potential to create an "inflammatory storm" that stimulates both innate and adaptive anti-tumor immune responses. The generation of anti-tumor immunity following OV treatment has been shown to be crucial for effective therapy. Therefore, establishing methodologies to measure the generation of anti-tumor T cell responses following OV infection in in vitro assays, which better mimic the complexity of the human tumor microenvironment (TME), will be critical to harness the full potential of OV therapy. Such experimental platforms will accelerate the development of next-generation OVs that are capable of overcoming immunosuppressive networks found within the tumor microenvironment. Here we describe a method that was designed to test the generation and quantification of human tumor-specific T cells following OV infection of 3D tumor spheroids cultured with or without fibroblasts.

摘要

溶瘤病毒(OVs)能在肿瘤细胞中快速且特异性地复制并杀死肿瘤细胞。OV对恶性细胞的靶向感染有可能引发“炎症风暴”,从而刺激先天性和适应性抗肿瘤免疫反应。OV治疗后产生抗肿瘤免疫已被证明对有效治疗至关重要。因此,建立在体外试验中测量OV感染后抗肿瘤T细胞反应产生的方法,该方法能更好地模拟人类肿瘤微环境(TME)的复杂性,对于充分发挥OV治疗的潜力至关重要。这样的实验平台将加速下一代OVs的开发,这些OVs能够克服肿瘤微环境中存在的免疫抑制网络。在此,我们描述一种方法,该方法旨在测试在用或不用成纤维细胞培养的3D肿瘤球体经OV感染后人类肿瘤特异性T细胞的产生和定量。

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Generation and Quantification of Cytotoxic Lymphocytes Following Oncolytic Virus Infection of Multi-cellular Tumor Spheroids.多细胞肿瘤球体溶瘤病毒感染后细胞毒性淋巴细胞的产生与定量
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