Immunomodulatory effects of tumor-associated fibroblasts in colorectal-tumor development

Int J Cancer. 1999 May 17;81(4):629-36. doi: 10.1002/(sici)1097-0215(19990517)81:4<629::aid-ijc20>;2-8.


In order to elucidate the role of myofibroblasts in tumor development, we compared fibroblastic reactions and their implications in the immune response in progressive and regressive rat colorectal-tumor models. Immunohistochemical analyses revealed that T lymphocytes and monocytes/macrophages were found outside progressive tumors that were surrounded by a large sheath of myofibroblasts. In vitro experiments using fibroblast- vs. myofibroblast-containing collagen gels showed that the mechanical properties of these tumor-activated myofibroblasts prevent penetration of T lymphocytes and macrophages within tumor nodules. These results indicate that tumor-activated myofibroblasts may prevent physical contact between cancer-cells and immune cells, an essential phenomenon for effective destruction of cancer cells. Successful immunotherapy against cancer should therefore include complementary treatments against these tumor-associated fibroblasts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1,2-Dimethylhydrazine
  • Adenocarcinoma / chemically induced
  • Adenocarcinoma / immunology*
  • Adenocarcinoma / pathology
  • Animals
  • Cell Division
  • Colonic Neoplasms / chemically induced
  • Colonic Neoplasms / immunology*
  • Colonic Neoplasms / pathology
  • Fibroblasts / immunology
  • Fibroblasts / pathology
  • Gene Transfer Techniques
  • Genetic Vectors
  • Interleukin-6 / genetics
  • Interleukin-6 / physiology*
  • Macrophages / immunology*
  • Macrophages / pathology
  • Monocytes / immunology
  • Monocytes / pathology
  • Neoplasm Invasiveness
  • Rats
  • Rats, Inbred Strains
  • Recombinant Proteins / biosynthesis
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology
  • Transfection
  • Tumor Cells, Cultured


  • Interleukin-6
  • Recombinant Proteins
  • 1,2-Dimethylhydrazine