Wu Heliang, Wang Yi, Lin Yulin, Ma Ru, Du Xuemei, Su Yandong, Yang Rui, Yang Zhiran, Liang Xinli, Zhang Yinguang, Liang Xiaoqing, Ji Zhonghe, Lai Chunning, Huang Yajing, Li Yan
Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Peking University Ninth School of Clinical Medicine, Beijing 100038, China.
Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
Cancer Biol Med. 2024 Nov 1;21(11):1078-94. doi: 10.20892/j.issn.2095-3941.2024.0218.
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 and efficacy of natural killer (NK) cells for treatment of MPM.
An 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 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.
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.
NK cell immunotherapy inhibited proliferation of MPM cells and with a good safety profile.
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的疗效。
进行一项体外研究，使用高内涵成像分析系统、细胞计数试剂盒-8检测法和瑞氏-吉姆萨染色评估脐带血来源的NK细胞对MPM细胞的细胞毒性。通过流式细胞术和酶联免疫吸附测定法检测NK细胞效应分子的表达水平。基于活细胞成像、透射电子显微镜和扫描电子显微镜确定NK细胞杀伤MPM细胞的能力。进行一项体内研究，基于实验性腹膜癌指数、小动物磁共振成像以及传统的组织病理学、细胞学和血液学研究评估NK细胞治疗的疗效和安全性。
NK细胞通过以剂量和密度依赖性方式释放效应分子（颗粒酶B、穿孔素、干扰素-γ和肿瘤坏死因子-α）有效杀伤MPM细胞。NK细胞的杀伤过程可能涉及四个动态步骤：趋化作用；撞击；黏附；以及穿透。NK细胞显著减轻了肿瘤负担，减少了腹水产生，并延长了生存时间，在NOG小鼠中无明显血液学毒性或器官损伤。
NK细胞免疫疗法抑制了MPM细胞的增殖，且安全性良好。
