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微生理模型揭示了记忆样自然杀伤细胞免疫疗法治疗 HIV 癌症的前景。

Microphysiological model reveals the promise of memory-like natural killer cell immunotherapy for HIV cancer.

机构信息

Department of Pathology & Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.

Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.

出版信息

Nat Commun. 2023 Oct 21;14(1):6681. doi: 10.1038/s41467-023-41625-8.

Abstract

Numerous studies are exploring the use of cell adoptive therapies to treat hematological malignancies as well as solid tumors. However, there are numerous factors that dampen the immune response, including viruses like human immunodeficiency virus. In this study, we leverage human-derived microphysiological models to reverse-engineer the HIV-immune system interaction and evaluate the potential of memory-like natural killer cells for HIV head and neck cancer, one of the most common tumors in patients living with human immunodeficiency virus. Here, we evaluate multiple aspects of the memory-like natural killer cell response in human-derived bioengineered environments, including immune cell extravasation, tumor penetration, tumor killing, T cell dependence, virus suppression, and compatibility with retroviral medication. Overall, these results suggest that memory-like natural killer cells are capable of operating without T cell assistance and could simultaneously destroy head and neck cancer cells as well as reduce viral latency.

摘要

许多研究都在探索使用细胞过继疗法来治疗血液系统恶性肿瘤和实体肿瘤。然而,有许多因素会抑制免疫反应,包括人类免疫缺陷病毒等病毒。在这项研究中,我们利用人源微生理模型来对 HIV-免疫相互作用进行逆向工程,并评估记忆样自然杀伤细胞在 HIV 头颈部癌症(HIV 感染者中最常见的肿瘤之一)中的潜力。在这里,我们评估了记忆样自然杀伤细胞在人源生物工程环境中的多个方面的反应,包括免疫细胞渗出、肿瘤穿透、肿瘤杀伤、T 细胞依赖性、病毒抑制以及与逆转录病毒药物的兼容性。总的来说,这些结果表明记忆样自然杀伤细胞能够在没有 T 细胞辅助的情况下发挥作用,并且可以同时破坏头颈部癌细胞并减少病毒潜伏。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/442b/10590421/277ca17e7c5f/41467_2023_41625_Fig1_HTML.jpg

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