The project leader aims to develop a highly interdisciplinary project (at the interface between bioinformatics and mathematical modelling, bench/hands-on research work and clinical input) based on computational analysis of immune-checkpoint receptors/molecules (ICR) and in vitro experimental validation to study the role of autophagy in monitoring the membrane expression of immune checkpoint receptors on peripheral (senescent) T cells. Further, we aim to identify potential correlations between autophagy levels and the membrane expression of these receptors on distinct peripheral T cell subsets, and identify, if any, the differences observed in older versus younger individuals. Nevertheless, the final aim is to investigate the changes in autophagy levels and ICR expression in T cells that occur as a result of colorectal cancer (CRC) in patients at the time of diagnosis, while considering age-matched healthy controls.
The long-term goal is to define the premises for understanding the dynamic relationship between autophagy and immunosenescence in T cells, and if or how modulating the autophagy process would be beneficial for improving the efficiency of immunotherapies in late-onset advanced CRC.
O1. To identify the immune-checkpoint molecules (both stimulatory and inhibitory) that act as
potential autophagic substrates and therefore whose membrane expressions may be chemically
manipulated by modulators of autophagy (with inhibitory or stimulatory effects).
O2. To define the basal autophagy levels in distinct subsets of T cell lymphocytes in healthy
individuals.
O3. To establish, if any, the correlation between the expression of previously identified ICR
(stimulatory or inhibitory) and autophagy levels in distinct subsets of T cells in healthy
individuals.
O4. To identify the potential changes in immune checkpoint expression and autophagy levels in
T cells caused by CRC in patients at the time of diagnosis.
OM – Managerial objectives.