ArticleBMC cancer2015
Cytotoxicity and infiltration of human NK cells in in vivo-like tumor spheroids.
Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 87 citations in OpenAlex.
- Natural Killer Cell Immunotherapy in Solid Tumors: Microenvironmental Obstacles and Translational 3D Models.Biology · 2026Review
- Podocalyxin may be down-regulated by progesterone in high grade serous ovarian cancer spheroids to increase responsiveness to carboplatin and NK cells.BMC cancer · 2026Article
- Cytokine preactivation and ADCC: a potent strategy for enhancing human NK cell effector functions against 3D tumor models.Frontiers in immunology · 2026Article
- Podocalyxin protects high grade serous ovarian cancer spheroids from NK cell infiltration and spheroid destruction.BMC cancer · 2025Article
- Combined IFN-γ and TNF-α treatment enhances the susceptibility of breast cancer cells and spheroids to Natural Killer cell-mediated killing.Cell death & disease · 2025Article
- A 3D tumor spheroid model with robust T cell infiltration for evaluating immune cell engagers.iScience · 2025Article
- The Activity of Human NK Cells Towards 3D Heterotypic Cellular Tumor Model of Breast Cancer.Cells · 2025Article
- A High-Throughput, Three-Dimensional Multiple Myeloma Model Recapitulating Tumor-Stroma Interactions for CAR-Immune Cell-Mediated Cytotoxicity Assay.ImmunoTargets and therapy · 2025Article
- A Review on Patient-derived 3D Micro Cancer Approach for Drug Screen in Personalized Cancer Medicine.Current cancer drug targets · 2025Review
- DNA origami assembled spheroid for evaluating cytotoxicity and infiltration of chimeric antigen receptor macrophage (CAR-M).Communications biology · 2024Article
- Organoid modeling meets cancers of female reproductive tract.Cell death discovery · 2024Review
- Anti-Mesothelin CAR-NK cells as a novel targeted therapy against cervical cancer.Frontiers in immunology · 2024Article
- Chitosan Cryogels Cross-Linked with 1,1,3-Triglycidyloxypropane: Mechanical Properties and Cytotoxicity for Cancer Cell 3D Cultures.Biomimetics (Basel, Switzerland) · 2023Article
- Tumor Organoid and Spheroid Models for Cervical Cancer.Cancers · 2023Review
- p‑STAT3 influences doxorubicin and etoposide resistance of A549 cells grown in anOncology reports · 2023Article
- Microphysiological systems for solid tumor immunotherapy: opportunities and challenges.Microsystems & nanoengineering · 2023Review
- Recent advances in microfluidic-based cancer immunotherapy-on-a-chip strategies.Biomicrofluidics · 2023Review
- γδ T cell-mediated cytotoxicity against patient-derived healthy and cancer cervical organoids.Frontiers in immunology · 2023Article
- Reovirus infection of tumor cells reduces the expression of NKG2D ligands, leading to impaired NK-cell cytotoxicity and functionality.Frontiers in immunology · 2023Article
- Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe complex cellular networks within tumors, the cytokine milieu, and tumor immune escape mechanisms affecting infiltration and anti-tumor activity of immune cells are of great interest to understand tumor formation and to decipher novel access points for cancer therapy. However, cellular in vitro assays, which rely on monolayer cultures of mammalian cell lines, neglect the three-dimensional architecture of a tumor, thus limiting their validity for the in vivo situation.
methodsThree-dimensional in vivo-like tumor spheroid were established from human cervical carcinoma cell lines as proof of concept to investigate infiltration and cytotoxicity of NK cells in a 96-well plate format, which is applicable for high-throughput screening. Tumor spheroids were monitored for NK cell infiltration and cytotoxicity by flow cytometry. Infiltrated NK cells, could be recovered by magnetic cell separation.
resultsThe tumor spheroids were stable over several days with minor alterations in phenotypic appearance. The tumor spheroids expressed high levels of cellular ligands for the natural killer (NK) group 2D receptor (NKG2D), mediating spheroid destruction by primary human NK cells. Interestingly, destruction of a three-dimensional tumor spheroid took much longer when compared to the parental monolayer cultures. Moreover, destruction of tumor spheroids was accompanied by infiltration of a fraction of NK cells, which could be recovered at high purity.
conclusionTumor spheroids represent a versatile in vivo-like model system to study cytotoxicity and infiltration of immune cells in high-throughput screening. This system might proof useful for the investigation of the modulatory potential of soluble factors and cells of the tumor microenvironment on immune cell activity as well as profiling of patient-/donor-derived immune cells to personalize cellular immunotherapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.