Lung Cancer Organoid System to Evaluate the Cytotoxicity of Natural Killer Cells
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Published on: February 22, 2020
Byungmoo Oh1,2, Jeongmin Kim1, Namwoog Kim1
1Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Korea.
Abstract:
Natural killer (NK) cells are gaining growing attention due to their promise for immunotherapy. A fast and accurate system is needed to test NK cell biology and their therapeutic application. Here, we report a lung cancer organoid-based system to evaluate NK cells' cytotoxicity. We first established the lung cancer organoids on top of Matrigel, which allows the co-culture with NK cells. When co-cultured, NK cells moved close to and inside the lung cancer organoids. When we analyzed by flow cytometry, co-culture of NK cells induced a significantly higher ratio of cell death of lung cancer organoids, suggesting that lung cancer organoids can be employed to test the cytotoxicity of NK cells. Finally, the pre-treatment of NK cells with A83-01, a TGFβ inhibitor, significantly enhanced the cell death of lung cancer organoids by NK cells, indicating that lung cancer organoid-based system faithfully recapitulates cell line-based system in evaluating the in vitro cytotoxicity of NK cells. These data represent that cancer organoid-based NK cell co-culture system is a reliable platform for studying NK cell biology and evaluating their cytotoxicity for screening for NK cell immunotherapy.
Insights
A new lung cancer organoid system effectively tests natural killer (NK) cell immunotherapy. This reliable platform accurately evaluates NK cell killing ability for potential cancer treatments.
Area of Science:
- Immunology
- Cancer Biology
- Biotechnology
Background:
- Natural killer (NK) cells show promise for cancer immunotherapy.
- A rapid and precise method is required to assess NK cell functions and therapeutic potential.
- Current methods may not fully represent the tumor microenvironment.
Purpose of the Study:
- To develop and validate a lung cancer organoid-based system for evaluating NK cell cytotoxicity.
- To assess the reliability of this system in recapitulating findings from traditional cell line models.
- To explore the potential of this platform for screening NK cell-based immunotherapies.
Main Methods:
- Lung cancer organoids were established on Matrigel for co-culture with NK cells.
- NK cell interaction with and infiltration into organoids were observed.
- Flow cytometry was used to quantify organoid cell death after co-culture.
- NK cells were pre-treated with a TGFβ inhibitor (A83-01) to assess its impact on cytotoxicity.
Main Results:
- NK cells demonstrated close proximity to and infiltration within lung cancer organoids.
- Co-culture with NK cells significantly increased lung cancer organoid cell death.
- The organoid system accurately reflected enhanced NK cell cytotoxicity upon TGFβ inhibition, mirroring cell line results.
- The system proved reliable for evaluating NK cell in vitro cytotoxicity.
Conclusions:
- A lung cancer organoid co-culture system provides a reliable platform for studying NK cell biology.
- This system can be effectively used to evaluate NK cell cytotoxicity for immunotherapy screening.
- The organoid model offers a more physiologically relevant approach compared to traditional cell lines.
