Ricerc@Sapienza

Immune checkpoint inhibitors (ICI) have radically changed the clinical course of many advanced solid tumors. In particular, PD-1 inhibitors interfere with the interaction between PD-1 and its ligand, expressed by tumor cells, inducing apoptosis.
Several recent evidences show that glucocorticoids (GCs) are able to increase PD-1 expression on lymphocytes and natural killer (NK) cells with an immunosuppressive effect. PD-1 activation, in fact, play a key role in maintaining immunological self-tolerance and inhibiting immune response. This effect seems to be also mediated by some cytokines (IL-12, IL-15 and IL-18) that are numerous in the tumor microenvironment.
Starting from this assumption, we designed a study aimed to investigate PD-1 expression on peripheral blood mononuclear cells (PBMC) and IL-12, IL-15 and IL-18 concentration in patients with Cushing's Syndrome (CS) compared with healthy controls. CS, indeed, represents a peculiar and unique prototype of endogenous GCs hypersecretion. Patients enrolled in the study will also undergo a complete hormonal assessment, infectious diseases and quality of sleep evaluation with proper and validated questionnaires.
The research, thus, moves from the clinical evidence of the immune suppression due to GCs, trying to better understand the underlying mechanisms in patients exposed to high levels of GCs, using CS as a model. This will be the first study considering the PD-1 expressions on the PBMC, and cytokines concentration in patients with CS, evaluating also metabolic profile, prevalence and severity of infectious disease and quality of sleep.
In brief, identifying the mechanisms underlying GC immunosuppression would allow a better understanding of the signs and numerous complications associated with CS, a target use of GCs therapy in patients who can benefit from it, avoiding exposing others to the numerous side effects. Finally, results can help to optimize the use of ICI in cancer therapy.