ABSTRACT

Microenvironment has a key role in tumor development, so that identification of stromal targets for cancer therapeutics is of great interest and could provide strategies that will complement therapies directed against cancer cells. The failure of immune surveillance to prevent tumor development and the observation that effective therapies can become ineffective over time suggest that mechanisms exist, whereby tumors can escape the immune system. TAFs, potentially originating from recruitment of resident tissue stem cells, bone marrow-derived mesenchymal stem cells (MSCs) or epithelial to mesenchymal transition within tumors, are important for tumor progression, providing both functional and structural supportive environment. The true origin, role, and biological characteristics of TAFs are not fully understood yet.
The main objective of our project is to fully characterize TAFs obtained from solid tumors (breast cancer), to establish their origin and role within the tumor stroma. MSCs will be used as normal/precursor cells to which the TAFs will be compared in order to identify specific marker, which would be used as target in prospective anti-tumor therapy designs. Cellular therapies in vitro prototype proposed by this project involves enhancement of human cytotoxic T lymphocytes (CTL) functionally active against TAF-derived specific antigen.

Keywords:

tumor associated fibroblasts (TAFs), mesenchymal stem cells (MSCs), cytotoxic T lymphocytes (CTL), molecular marker, specific antigen