Browsing by Author "Peura, Aino"

Breast cancer is the most common cancer among women and the second most leading cause of cancer related deaths in Finland, accounting for over 900 deaths annually. The majority of breast cancer related fatalities are caused by therapy resistance leading to metastasis. Several studies have established the role of soft matrix in promoting the undifferentiated and oestrogen receptor negative phenotype of breast cancer cells, which are also resistant to a variety of commonly used chemotherapeutics and hormonal therapies. On the contrary, traditionally tumor tissue is has been considered as extremely stiff, and the stiffness of the tumor microenvironment has been established to promote the growth and the metastasis of several cancer types. In this study we adressed how microenvironmental stiffness alters the phenotype of antitumor immune response by culturing primary breast tumor tissue in PDEC-model. We established, that the soft microenvironment promotes immune suppression in primary breast cancer by upregulating the production of immuno suppressive cytokines and polarizating macrophages towards more M2 or alternatively activated ones. Moreover, in the soft microenvironment, cytotoxic CD8+ T-cells are lost. These effects are created by tumor tissue derived paracrine signaling and by inhibiting these signals with small molecules we were able to reverse the observed immunosuppression. These results provide us a novel information how microenvironmental stiffness alters the phenotype of the antitumor immune response