Immunomodulatory effects of tumor-associated fibroblasts in colorectal-tumor development.
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.
Lieubeau
B
B
INSERM U419, Institut de Biologie, Nantes, France.
Heymann
M F
MF
Henry
F
F
Barbieux
I
I
Meflah
K
K
Grégoire
M
M
D019813:1,2-Dimethylhydrazine; D000230:Adenocarcinoma / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D000818:Animals; D002455:Cell Division; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D005347:Fibroblasts / Q000276:immunology / Q000473:pathology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D009361:Neoplasm Invasiveness; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; D011994:Recombinant Proteins; D019813:1,2-Dimethylhydrazine