Potential treatment approaches for malignant peritoneal mesothelioma: in vivo and in vitro experimental study of natural killer cell immunotherapy

Our plain-English summary of Potential treatment approaches for malignant peritoneal mesothelioma: in vivo and in vitro experimental study of natural killer cell immunotherapy, by H. Wu, Y. Wang, Y. Lin, et al (Cancer Biology & Medicine, 2024).

The study

• Authors: H. Wu, Y. Wang, Y. Lin, R. Ma, X. Du, Y. Su, R. Yang, Z. Yang, X. Liang, Y. Zhang, X. Liang, Z. Ji, C. Lai, Y. Huang, Y. Li
• Journal: Cancer Biology & Medicine
• Published: 2024;21(11):1078-94
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

Copyright © 2024 The Authors.

In plain English

This laboratory and animal study from Beijing, China, tested whether natural killer (NK) cells grown from umbilical cord blood could kill malignant peritoneal mesothelioma (MPM) cells. NK cells are a type of immune cell. The MPM cells came from patients' surgical tumor specimens that had been grown in mice. The study did not look at asbestos exposure. In laboratory dishes, more NK cells killed more MPM cells. After 24 hours, killing rates were 92.73%, 70.02% and 49.74% at NK-to-tumor-cell ratios of 20:1, 10:1 and 5:1. Killing fell as the tumor cells grew denser: at the densest level the rates were 48.91%, 35.19% and 7.50%. Twenty mice were injected with MPM cells. Ten then received four weekly NK cell injections and ten received saline. Tumor spread scores were much lower in the NK group. Bloody abdominal fluid appeared in 5 of 10 control mice and 0 of 10 NK-treated mice. Of the five mice per group followed to day 50, all controls reached humane endpoints, while the NK-treated mice remained well. Blood, liver and kidney tests showed no significant group differences. The authors called the findings preliminary and said they lay groundwork for clinical studies.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) experiments on human MPM cells plus an animal experiment in mice (in vivo)
• Who was studied: Primary MPM cells from patient-derived xenograft models built from MPM surgical specimens; 20 NOG mice (4 to 5 weeks old), randomly split into control and NK cell treatment groups of 10 each; work done in Beijing, China
• Exposure: Not an asbestos exposure study. The treatment studied was umbilical cord blood-derived NK cells. In mice: intraperitoneal injection of 2 × 10^7 NK cells on day 2, then every 7 days for a total of 4 injections. Control mice received an equivalent volume of saline. In dishes, NK-to-MPM cell ratios ranged from 20:1 down to 0:1.
• Main results:
  • In dishes, at the single-cell level after 24 hours, NK cells killed 92.73%, 70.02% and 49.74% of MPM cells at 20:1, 10:1 and 5:1 ratios
  • At the single tumor cell colony level, 24-hour lysis rates at 20:1, 10:1 and 5:1 ratios were 73.70%, 56.07% and 31.26%
  • At the large tumor cell confluence (densest) level, lysis rates were 48.91%, 35.19% and 7.50%
  • In NK cells after 24 hours of co-culture with MPM cells, levels of CD107, granzyme B, perforin, IFN-γ and TNF-α expression were significantly increased
  • In mice, the experimental peritoneal cancer index (tumor spread score) was much lower in the NK group than in the control group
  • Within the 50-day follow-up, bloody ascites occurred in 5 of 10 control mice (50%) and 0 of 10 NK-group mice
  • Five mice per group were examined on day 30, and the remaining five per group were observed for survival. By the time the experiment ended on day 50, all control mice in this survival group had reached humane endpoints, while all NK-group mice remained well and active.
  • On day 30, routine blood tests and liver and kidney function tests showed no significant differences between the NK and control groups
  • Organ tissue examination showed no obvious focal necrosis or lymphocyte infiltration in either group
• The authors' conclusion: The authors concluded that NK cells showed therapeutic efficacy in the MPM patient-derived xenograft model without signs of systemic toxicity, laying groundwork for clinical studies. They described the findings as preliminary evidence.
• Limitations the authors state:
  • The authors described their findings as preliminary evidence
  • The authors said further work is needed: on why some tumor cells escape, on the cell-in-cell killing mechanism, on why tumor-infiltrating NK cells lose function, and on the dose, mode and timing of NK cell infusion

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Immunotherapy, Prognosis, Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), Peritoneal Cancer Index (PCI), Necrosis, Tumor Burden.

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• Asbestos and cancer: human natural killer cell activity is suppressed by asbestos fibers but can be restored by recombinant interleukin-2 — B.W. Robinson (1989)
• Natural killer cell activity in asbestos workers. Interactive effects of smoking and asbestos exposure — R.D. deShazo, J. Morgan, et al. (1988)
• Effects of in vitro asbestos exposure on natural killer and antibody-dependent cellular cytotoxicity — R.G. Barbers, J. Oishi (1987)
• Functional Alteration of Natural Killer Cells and Cytotoxic T Lymphocytes upon Asbestos Exposure and in Malignant Mesothelioma Patients — Y. Nishimura, N. Kumagai-Takei, et al. (2015)

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