RANK pathway as a key regulator of the tumour-immune crosstalk and tumour immunity

Abstract

[eng] OBJECTIVES: In this thesis we aim to demonstrate that Rank expression in tumour or myeloid cells promotes an immunosuppressive microenvironment that favours the tumour onset and progression. To address this hypothesis, the specific objectives are: 1. To determine how RANK expression in breast cancer cells regulates the tumour-immune response and tumour onset. 1.1 To evaluate the intrinsic effects of the loss of Rank expression in tumour cells in an immunodeficient environment. 1.2 To evaluate how Rank overexpression in tumour cells regulates the tumour- immune crosstalk in breast cancer. 2. To determine whether and how RANK expression in macrophages regulates the tumour-immune response and its therapeutic impact on breast cancer. 2.1 To investigate the role of RANK in macrophage differentiation and activation.

2.2 To evaluate whether the loss of Rank expression in macrophages modulates its functionality in a tumour setting and its implication in breast cancer. 2.3 To evaluate the therapeutic benefit of the systemic inhibition of Rank signalling and its impact on macrophage functionality.