Evidence map›Paper›PMID 34572807›Full record

ArticleCancers2021

3D Model of the Early Melanoma Microenvironment Captures Macrophage Transition into a Tumor-Promoting Phenotype.

Gabriela A Pizzurro, Chang Liu, Kathryn Bridges, Amanda F Alexander, Alice Huang, Janani P Baskaran, Julie Ramseier, Marcus W Bosenberg, Michael Mak, Kathryn Miller-Jensen

Abstract read
In one paragraph

Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Tumor Microenvironment in Melanoma-Characteristic and Clinical Implications.International journal of molecular sciences · 2025
    Review
  5. Enhancing Transcutaneous Drug Delivery: Advanced Perspectives on Skin Models.JID innovations : skin science from molecules to population health · 2025
    Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Gabriela A PizzurroDepartment of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
Chang LiuDepartment of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
Kathryn BridgesDepartment of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
Amanda F AlexanderDepartment of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
Alice HuangDepartment of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
Janani P BaskaranDepartment of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.ORCID 0000-0002-4764-9611
Julie RamseierDepartment of Dermatology, Yale University, New Haven, CT 06511, USA.ORCID 0000-0002-6383-9837
Marcus W BosenbergDepartment of Dermatology, Yale University, New Haven, CT 06511, USA.
Michael MakDepartment of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.
Kathryn Miller-JensenDepartment of Biomedical Engineering, Yale University, New Haven, CT 06511, USA.

Funding

Yale SPORE in Skin CancerP50CA121974 · NCI · YALE UNIVERSITY · PI MARCUS W BOSENBERG, Harriet M. Kluger · 2006 to 2026
$43.9M
(PQ5) Mitochondrial Heterogeneity in Melanoma Tumor and Immune ResponsesR01CA216101 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI GERALD SHADEL · 2018 to 2026
$5.0M
Systems analysis of cell-cell communication networks and immune activity in the melanoma tumor microenvironmentU01CA238728 · NCI · YALE UNIVERSITY · PI BOSENBERG, MARCUS W, MILLER-JENSEN, KATHRYN · 2020 to 2024
$2.9M
Harry J. Lloyd Charitable Trust Melanoma Research GrantNCI NIH HHS P50 CA121974NCI NIH HHS R01 CA216101NCI NIH HHS U01 CA238728
6 · The paper itself

Abstract

Tumor immune response is shaped by the tumor microenvironment (TME), which often evolves to be immunosuppressive, promoting disease progression and metastasis. An important example is melanoma tumors, which display high numbers of tumor-associated macrophages (TAMs) that are immunosuppressive but also have the potential to restore anti-tumor activity. However, to therapeutically target TAMs, there is a need to understand the early events that shape their tumor-promoting profile. To address this, we built and optimized 3D in vitro co-culture systems, composed of a collagen-I matrix scaffolding murine bone-marrow-derived macrophages (BMDMs), YUMM1.7 melanoma cells, and fibroblasts to recreate the early melanoma TME and study how interactions with fibroblasts and tumor cells modulate macrophage immune activity. We monitored BMDM behavior and interactions through time-lapse imaging and characterized their activation and secretion. We found that stromal cells induced a rapid functional activation, with increased motility and response from BMDMs. Over the course of seven days, BMDMs acquired a phenotype and secretion profile that resembled melanoma TAMs in established tumors. Overall, the direct cell-cell interactions with the stromal components in a 3D environment shape BMDM transition to a TAM-like immunosuppressive state. Our systems will enable future studies of changes in macrophage-stromal cross-talk in the melanoma TME.

Indexed as

3D culturefibroblastsimmunosuppressionmelanomatumor-associated macrophagestumor microenvironmenttype I collagen

Identifiers

PMID34572807
PMCPMC8471848

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Registered trials

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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.