Heliang Wu, Yi Wang, Yulin Lin, Ru Ma, Xuemei Du, Yandong Su, Rui Yang, Zhiran Yang, Xinli Liang, Yinguang Zhang, Xiaoqing Liang, Zhonghe Ji, Chunning Lai, Yajing Huang, Yan Li
{"title":"Potential treatment approaches for malignant peritoneal mesothelioma: in vivo and in vitro experimental study of natural killer cell immunotherapy.","authors":"Heliang Wu, Yi Wang, Yulin Lin, Ru Ma, Xuemei Du, Yandong Su, Rui Yang, Zhiran Yang, Xinli Liang, Yinguang Zhang, Xiaoqing Liang, Zhonghe Ji, Chunning Lai, Yajing Huang, Yan Li","doi":"10.20892/j.issn.2095-3941.2024.0218","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Malignant peritoneal mesothelioma (MPM) is a rare primary malignant tumor with an extremely poor prognosis that currently lacks effective treatment options. This study investigated the <i>in vitro</i> and <i>in vivo</i> efficacy of natural killer (NK) cells for treatment of MPM.</p><p><strong>Methods: </strong>An <i>in vitro</i> study was conducted to assess the cytotoxicity of NK cells from umbilical cord blood to MPM cells with the use of a high-content imaging analysis system, the Cell Counting Kit-8 assay, and Wright-Giemsa staining. The level of NK cell effector molecule expression was detected by flow cytometry and enzyme-linked immunosorbent assays. The ability of NK cells to kill MPM cells was determined based on live cell imaging, transmission electron microscopy, and scanning electron microscopy. An <i>in vivo</i> study was conducted to assess the efficacy and safety of NK cell therapy based on the experimental peritoneal cancer index, small animal magnetic resonance imaging, and conventional histopathologic, cytologic, and hematologic studies.</p><p><strong>Results: </strong>NK cells effectively killed MPM cells through the release of effector molecules (granzyme B, perforin, interferon-γ, and tumor necrosis factor-α) in a dose- and density-dependent manner. The NK cell killing process potentially involved four dynamic steps: chemotaxis; hitting; adhesion; and penetration. NK cells significantly reduced the tumor burden, diminished ascites production, and extended survival with no significant hematologic toxicity or organ damage in NOG mice.</p><p><strong>Conclusions: </strong>NK cell immunotherapy inhibited proliferation of MPM cells <i>in vitro</i> and <i>in vivo</i> with a good safety profile.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":null,"pages":null},"PeriodicalIF":5.6000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Biology & Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.20892/j.issn.2095-3941.2024.0218","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: Malignant peritoneal mesothelioma (MPM) is a rare primary malignant tumor with an extremely poor prognosis that currently lacks effective treatment options. This study investigated the in vitro and in vivo efficacy of natural killer (NK) cells for treatment of MPM.
Methods: An in vitro study was conducted to assess the cytotoxicity of NK cells from umbilical cord blood to MPM cells with the use of a high-content imaging analysis system, the Cell Counting Kit-8 assay, and Wright-Giemsa staining. The level of NK cell effector molecule expression was detected by flow cytometry and enzyme-linked immunosorbent assays. The ability of NK cells to kill MPM cells was determined based on live cell imaging, transmission electron microscopy, and scanning electron microscopy. An in vivo study was conducted to assess the efficacy and safety of NK cell therapy based on the experimental peritoneal cancer index, small animal magnetic resonance imaging, and conventional histopathologic, cytologic, and hematologic studies.
Results: NK cells effectively killed MPM cells through the release of effector molecules (granzyme B, perforin, interferon-γ, and tumor necrosis factor-α) in a dose- and density-dependent manner. The NK cell killing process potentially involved four dynamic steps: chemotaxis; hitting; adhesion; and penetration. NK cells significantly reduced the tumor burden, diminished ascites production, and extended survival with no significant hematologic toxicity or organ damage in NOG mice.
Conclusions: NK cell immunotherapy inhibited proliferation of MPM cells in vitro and in vivo with a good safety profile.
目的:恶性腹膜间皮瘤(MPM)是一种罕见的原发性恶性肿瘤,预后极差,目前缺乏有效的治疗方案。本研究调查了自然杀伤(NK)细胞治疗 MPM 的体外和体内疗效:方法:采用高内涵成像分析系统、细胞计数试剂盒-8检测法和赖特-吉氏染色法进行体外研究,评估脐带血中的NK细胞对骨髓瘤细胞的细胞毒性。流式细胞术和酶联免疫吸附试验检测了 NK 细胞效应分子的表达水平。通过活细胞成像、透射电子显微镜和扫描电子显微镜确定了 NK 细胞杀死 MPM 细胞的能力。根据实验性腹膜癌指数、小动物磁共振成像以及常规组织病理学、细胞学和血液学研究,进行了一项体内研究,以评估 NK 细胞疗法的有效性和安全性:结果:NK细胞通过释放效应分子(颗粒酶B、穿孔素、干扰素-γ和肿瘤坏死因子-α)以剂量和密度依赖的方式有效杀死了MPM细胞。NK 细胞的杀伤过程可能涉及四个动态步骤:趋化、打击、粘附和穿透。NK细胞明显减轻了NOG小鼠的肿瘤负荷,减少了腹水的产生,延长了小鼠的生存期,而且没有明显的血液学毒性或器官损伤:结论:NK细胞免疫疗法在体外和体内均能抑制MPM细胞的增殖,安全性良好。
期刊介绍:
Cancer Biology & Medicine (ISSN 2095-3941) is a peer-reviewed open-access journal of Chinese Anti-cancer Association (CACA), which is the leading professional society of oncology in China. The journal quarterly provides innovative and significant information on biological basis of cancer, cancer microenvironment, translational cancer research, and all aspects of clinical cancer research. The journal also publishes significant perspectives on indigenous cancer types in China.