MOLECULAR BASES OF PROGESTERONE-INDUCED IMMUNESUPPRESSION IN BREAST CANCER

SALATINO M,

Buenos Aires

Conferencia; SAB 2009 Sociedad Argentina de Biologia; 2009

Compelling data support the view that the immune system is essential for the control of tumor development and growth. However, tumor cells employ a diversity of mechanisms that circumvent antitumor responses. These mechanisms include the secretion of immunosuppressive factors as galectin-1 and TGF-b and the expansion and/or recruitment of suppressor cells as CD4+-CD25+-Foxp3+ regulatory T (Tregs) cells. Based on the tolerogenic properties of progesterone, and its promoting role in breast cancer, we investigated whether progesterone may create an immune privileged microenvironment in breast cancer, either by regulating galectin-1 expression or controlling Tregs differentiation. The progesterone analogue medroxiprogesterone acetate (MPA) was able of inducing galectin-1 expression in two hormone-dependent human breast cancer cell lines and in a mouse mammary tumor. Interestingly, in vitro MPA-treatment of mouse splenocytes or human PBMC induced a significant increase in the frequency of Tregs and skewed the balance toward a Th2-type cytokine profile. In vivo MPA-treatment increased the frequency of Tregs in tumor-draining lymph nodes and within the tumor. MPA-induction of Tregs was associated with an effect both on CCL22 chemokine and on TGF -b pathway. Our results showed that progesterone fosters an immunosuppressive tumor stroma by regulating galectin-1 expression and augmenting the frequency of Tregs in breast cancer.