ArticlePloS one2012
Integrating macrophages into organotypic co-cultures: a 3D in vitro model to study tumor-associated macrophages.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 115 citations in OpenAlex.
- Establishment of extrahepatic bile duct cancer organoids using suspension culture and their application in clinical drug screening.Oncology letters · 2026Article
- Using biomaterial-based 3D in vitro cancer models to solve current clinical problems.British journal of cancer · 2026Review
- Tumor Organoid and Microenvironment Cocultures: Implications for Basic and Translational Cancer Research.MedComm · 2026Review
- Article
- Tumor organoid-immune co-culture models: exploring a new perspective of tumor immunity.Cell death discovery · 2025Review
- Replicating Dynamic Immune Responses at Single-Cell Resolution within a Microfluidic Human Skin Equivalent.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- From neglect to necessity: the role of innate immunity in cutaneous squamous cell carcinoma therapy.Frontiers in immunology · 2025Review
- Editorial: Women in cytokines and soluble mediators in immunity.Frontiers in immunology · 2024Article
- In vitro co-culture models for studying organoids-macrophages interaction: the golden technology of cancer immunotherapy.American journal of cancer research · 2024Review
- Article
- Modeling immunity in microphysiological systems.Experimental biology and medicine (Maywood, N.J.) · 2023Review
- Probing organoid metabolism using fluorescence lifetime imaging microscopy (FLIM): The next frontier of drug discovery and disease understanding.Advanced drug delivery reviews · 2023Review
- The Three-Dimensional In Vitro Cell Culture Models in the Study of Oral Cancer Immune Microenvironment.Cancers · 2023Review
- Macrophage Profiling in Head and Neck Cancer to Improve Patient Prognosis and Assessment of Cancer Cell-Macrophage Interactions Using Three-Dimensional Coculture Models.International journal of molecular sciences · 2023Article
- Article
- Towards using 3D cellular cultures to model the activation and diverse functions of macrophages.Biochemical Society transactions · 2023Review
- The role of macrophages in non-small cell lung cancer and advancements in 3D co-cultures.eLife · 2023Article
- Dendritic cell phenotype and function in a 3D co-culture model of patient-derived metastatic colorectal cancer organoids.Frontiers in immunology · 2023Article
- Monocytes and T cells incorporated in full skin equivalents to study innate or adaptive immune reactions after burn injury.Frontiers in immunology · 2023Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor progression is controlled by signals from cellular and extra-cellular microenvironment including stromal cells and the extracellular matrix. Consequently, three-dimensional in vitro tumor models are essential to study the interaction of tumor cells with their microenvironment appropriately in a biologically relevant manner. We have previously used organotypic co-cultures to analyze the malignant growth of human squamous cell carcinoma (SCC) cell lines on a stromal equivalent in vitro. In this model, SCC cell lines are grown on a collagen-I gel containing fibroblasts. Since macrophages play a critical role in the progression of many tumor types, we now have expanded this model by integrating macrophages into the collagen gel of these organotypic tumor co-cultures. This model was established as a murine and a human system of skin SCCs. The effect of macrophages on tumor progression depends on their polarization. We demonstrate that macrophage polarization in organotypic co-cultures can be modulated towards and M1 or an M2 phenotype by adding recombinant IFN-γ and LPS or IL-4 respectively to the growth medium. IL-4 stimulation of macrophage-containing cultures resulted in enhanced tumor cell invasion evidenced by degradation of the basement membrane, enhanced collagenolytic activity and increased MMP-2 and MMP-9. Interestingly, extended co-culture with tumor cells for three weeks resulted in spontaneous M2 polarization of macrophages without IL-4 treatment. Thus, we demonstrate that macrophages can be successfully integrated into organotypic co-cultures of murine or human skin SCCs and that this model can be exploited to analyze macrophage activation towards a tumor supporting phenotype.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.