Improvement of
immunotherapy-based protocols in
cancer requires a better understanding of tumor microenvironment and
tumor-host interaction. Stromal and immune cells and molecules such as
cytokines,
chemokines,
growth factors and
metalloproteases mediate
tumor-host interaction determining, at least in part,
tumor development. In the present study, we used an immunohistochemical approach to explore leukocyte sub-populations,
cytokine profiles and costimulatory molecule expression in rat N -
Nitrosomethylurea (NMU)-induced
breast tumors. Our results show a strong leukocyte infiltration mainly composed of macrophages and TCR alphabeta positive T cells. We observed a weak expression of costimulatory molecules (CD80, CD86) and an absence of inflammatory
cytokines (IFNgamma,
TNFalpha, IP-10) and lymphocyte activation markers (CD25). Interestingly, this immunosuppressed status could be a consequence of
IL-10 expression by malignant cells, as demonstrated by immunohistology and western blot analysis, which seems to be an early event during mammary
carcinogenesis. Analysis of a cell line derived from an NMU-induced rat
breast tumor showed that this cell line also expresses
IL-10. This study shows that the NMU model of rat
breast cancer could be used to evaluate different immune based
therapies as well as to study the role of
IL-10 in
breast cancer. Furthermore, this rat
breast cancer model shows an immunohistological profile similar to that found in human
cancer and the fact that it develops like spontaneously arising
malignancies make it interesting as a
cancer model in immunobiology.