Immunobiological characterization of N -nitrosomethylurea-induced rat breast carcinomas: tumoral IL-10 expression as a possible immune escape mechanism.

ABSTRACT

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.