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Updated: Jul 23, 2025

Measurement of Natural Killer Cell-Mediated Cytotoxicity and Migration in the Context of Hepatic Tumor Cells
Published on: February 22, 2020
In vitro models to study natural killer cell dynamics in the tumor microenvironment
Valentina Carannante1, Martin Wiklund1, Björn Önfelt1,2
1Department of Applied Physics, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
Abstract:
Immunotherapy is revolutionizing cancer therapy. The rapid development of new immunotherapeutic strategies to treat solid tumors is posing new challenges for preclinical research, demanding novel in vitro methods to test treatments. Such methods should meet specific requirements, such as enabling the evaluation of immune cell responses like cytotoxicity or cytokine release, and infiltration into the tumor microenvironment using cancer models representative of the original disease. They should allow high-throughput and high-content analysis, to evaluate the efficacy of treatments and understand immune-evasion processes to facilitate development of new therapeutic targets. Ideally, they should be suitable for personalized immunotherapy testing, providing information for patient stratification. Consequently, the application of in vitro 3-dimensional (3D) cell culture models, such as tumor spheroids and organoids, is rapidly expanding in the immunotherapeutic field, coupled with the development of novel imaging-based techniques and -omic analysis. In this paper, we review the recent advances in the development of in vitro 3D platforms applied to natural killer (NK) cell-based cancer immunotherapy studies, highlighting the benefits and limitations of the current methods, and discuss new concepts and future directions of the field.
Insights
Novel 3D cell culture models are advancing preclinical cancer immunotherapy research. These advanced in vitro methods, particularly for natural killer (NK) cell therapies, improve treatment evaluation and target discovery.
Area of Science:
- Cancer Research
- Immunotherapy
- Preclinical Models
Background:
- Immunotherapy is transforming cancer treatment, necessitating advanced preclinical research methods for solid tumors.
- Current in vitro models face challenges in evaluating complex immune responses and tumor microenvironment interactions.
Purpose of the Study:
- To review recent advances in in vitro 3D platforms for natural killer (NK) cell-based cancer immunotherapy.
- To highlight the benefits and limitations of current 3D models in preclinical immunotherapy studies.
- To discuss future directions for in vitro 3D platforms in personalized cancer immunotherapy.
Main Methods:
- Review of in vitro 3-dimensional (3D) cell culture models, including tumor spheroids and organoids.
- Integration of novel imaging-based techniques and omics analysis with 3D models.
- Focus on applications in natural killer (NK) cell immunotherapy research.
Main Results:
- In vitro 3D models like spheroids and organoids are increasingly used in immunotherapy research.
- These models facilitate evaluation of immune cell cytotoxicity, cytokine release, and tumor infiltration.
- 3D platforms enable high-throughput, high-content analysis for treatment efficacy and immune evasion studies.
Conclusions:
- In vitro 3D platforms are crucial for advancing preclinical cancer immunotherapy, especially NK cell-based strategies.
- These models offer improved representation of the tumor microenvironment and immune responses.
- Further development is needed to fully realize the potential of 3D models for personalized immunotherapy.

