SenePhagy project aims to characterize the role of autophagy in monitoring the expression of immune-checkpoint receptors (ICR) on peripheral (senescent) T cells with implications in the colorectal cancer (CRC). CRC are frequently diagnosed in elderly individuals and are characterized by a gradual decline of immune functions known as immunosenescence. This age-related process leads to the loss of T cells’ anti-tumor response, resulting in decreased effectiveness of immunotherapies, including immune-checkpoint inhibitors. The development of strategies to overcome these T cell imbalances are crucial for enhancing the therapeutic outcome in CRC patients.
Autophagy is an evolutionarily intracellular degradative pathway that is preeminent to the cellular and organismal homeostasis. Since autophagy may also degrade cellular receptors, the novel approach we are introducing, of manipulating the surface expression of ICR on T cells via autophagy, would be key in defining strategies for amplifying the T cells’ anti-tumor activity.
We are proposing to develop a project that requires multidisciplinary expertise at the interface between bioinformatics, bench research and clinical input. Initially, we shall identify by bioinformatics analysis the ICR acting as autophagy substrates, followed by in vitro validation (flow-cytometry analysis of T cell subsets (naïve, memory), detection of autophagy levels) using peripheral CD4+ T and CD8+ T cells isolated from healthy controls and CRC patients.