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Related Concept Videos

The Tumor Microenvironment02:17

The Tumor Microenvironment

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Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
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Related Experiment Video

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A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth
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A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth

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Melanoma-associated fibroblasts decrease tumor cell susceptibility to NK cell-mediated killing through

Linda Ziani1,2,3, Thouraya Ben Safta-Saadoun1,2,3, Johanne Gourbeix1,2

  • 1INSERM, UMR 1186, Villejuif, France.

Oncotarget
|April 21, 2017
PubMed
Summary
This summary is machine-generated.

Cancer-associated fibroblasts (CAFs) reduce natural killer (NK) cell activity against melanoma by secreting matrix metalloproteinases. This process lowers tumor cell susceptibility to NK-mediated killing, impacting anti-tumor immunity.

Keywords:
MICA/Bcancer-associated fibroblastsmatrix-metalloproteinasesmelanomanatural killer cells

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Area of Science:

  • Immunology
  • Oncology
  • Cancer Biology

Background:

  • Cancer-associated fibroblasts (CAFs) are key players in tumor-stroma interactions, promoting tumor growth.
  • CAFs influence the anti-tumor immune response by secreting factors that affect immune cells within the tumor microenvironment.
  • The precise mechanisms by which CAFs modulate immune responses are not fully understood.

Purpose of the Study:

  • To investigate how melanoma-associated fibroblasts (MAFs) affect the susceptibility of melanoma cells to natural killer (NK) cell-mediated lysis.
  • To elucidate the molecular mechanisms underlying MAF-induced immune evasion in melanoma.

Main Methods:

  • Co-culture experiments involving melanoma cells and MAFs.
  • Analysis of matrix metalloproteinase (MMP) secretion by MAFs.
  • Assessment of NKG2D ligand expression (MICA/B) on melanoma cells.
  • Measurement of NK cell cytotoxic activity against melanoma cells.

Main Results:

  • MAFs secrete active matrix metalloproteinases (MMPs).
  • MMP secretion by MAFs reduces the expression of NKG2D ligands (MICA/B) on melanoma tumor cells.
  • This reduction in NKG2D ligands leads to decreased NK cell-mediated lysis of melanoma cells.

Conclusions:

  • Melanoma-associated fibroblasts diminish tumor cell susceptibility to NK cell killing through MMP secretion.
  • The downregulation of NKG2D ligands on tumor cells is a critical mechanism by which MAFs impair NK cell anti-tumor activity.
  • Modification of tumor cell sensitivity to cytotoxic cells is a significant factor in CAF-mediated immune evasion.