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

In order to elucidate the role of myofibroblasts in tumor development, we c ompared fibroblastic reactions and their implications in the immune respons e in progressive and regressive rat colorectal-tumor models. Immunohistoche mical analyses revealed that T lymphocytes and monocytes/macrophages were f ound outside progressive tumors that were surrounded by a large sheath of m yofibroblasts. In vitro experiments using fibroblast- vs. myofibroblast-con taining collagen gels showed that the mechanical properties of these tumor- activated myofibroblasts prevent penetration of T lymphocytes and macrophag es within tumor nodules. These results indicate that tumor-activated myofib roblasts may prevent physical contact between cancer-cells and immune cells , an essential phenomenon for effective destruction of cancer cells. Succes sful immunotherapy against cancer should therefore include complementary tr eatments against these tumor-associated fibroblasts. (C) 1999 Wiley-Liss, I nc.