To decode Treg signatures in cancer in order to:

• Develop a Treg-based “liquid” biopsy to predict response to immunotherapy & autoimmune side effects.
• Generate innovative tools for identification & validation of therapeutic targets.

Project Overview

Immunotherapy has revolutionized cancer treatment. However, more than half of treated patients do not show beneficial clinical outcomes whereas responses are often accompanied by severe autoimmune side effects. Predictive biomarkers of clinical response and novel approaches to master anti-tumor immunity while keeping in check autoimmune responses are very important challenges in oncology that can open the path to effective treatment of cancer.
It is the ambition of REGSIGN to answer fundamental research questions and provide diagnostic tools to improve the quality of care for cancer patients. RegSign through multi-parametric single-cell analysis will set the stage for exploring novel concepts in cancer, such as the role of circulating regulatory T cells, that represent one of the main obstacles for effective immunotherapies, to serve as a “liquid” biopsy for predicting response to treatment and development of autoimmune manifestations. Furthermore, this project will generate innovative animal models, that will allow the development and testing of new immunotherapeutic targets and design of personalized therapy.  Finally, RegSign will tackle with a pioneering concept of modulating Treg metabolism to adjuvant immune system to fight cancer and simultaneously keep in track hazardous attacks on self tissue, that will generate breakthroughs in management of immunotherapy-induced autoimmune side effects.

A multi-parametric Regulatory T cell Atlas in cancer to predict immunotherapy response, adverse autoimmune events and to identify novel therapeutic targets

Project Overview

Autoimmune Diseases (ADs) affect approximately 40 million people worldwide, which translates into a total cost of several billion Euros per year deriving from their clinical management and the associated loss in work productivity. Clearly, based on these figures, the potential for societal impact of a commensurate action targeting ADs is extraordinary. The market for inflammatory diseases represents one of the fastest growing areas of pharmaceutical industry. Although biologic interventions targeting components of the immune response have replaced the generalized immunosuppressive strategies in the treatment of ADs, a significant portion of patients fails to achieve true remission. Therefore there is an increased interest in exploring strategies to provide long term disease suppression.
AutoReg intends to broaden our knowledge beyond the state of the art, using ground-breaking approaches in order to provide a comprehensive analysis of the mechanisms dictating Treg dysfunction during development of autoimmune responses that represent one of the main obstacles towards designing effective immunotherapies. Our findings will pave the way for the development of therapeutic protocols that exploit Tregs for the treatment of autoimmunity as well as diseases in which disturbed tolerance is a common denominator. Based on our solid preliminary data that highlight significant alterations in the mitochondrial function and the nature of Tregs in autoimmune mice and in patients with autoimmune manifestations, we propose to target Treg mitochondria function for therapeutic intervention of autoimmune responses. Furthermore, AutoReg will generate innovative tools for a) restoring Treg mitochondrial function such as the cutting edge generation of unique conditional knockin animal models and b) development of exclusive in vitro models to study immunotherapy induced toxicities.

AutoReg: Dissecting the Regulatory T cell metabolic aberrancies in autoimmunity to empower their function.