Ricerc@Sapienza

Background: The use of immune checkpoint inhibitors in the treatments of cancer patients, is a consolidated and effective therapy that has been associated with different toxicities, defined Immune-related Adverse Events (IrAEs). Reports of IrAEs describe symptoms resembling classic rheumatic diseases, most notably associated with cytotoxic T-lymphocyte-associated protein 4 inhibitor blockade. There are fewer reports of rheumatic diseases associated to treatment with programmed cell death protein-1 (PD-1) and its ligand (PD-L1) inhibitors, even if cases have been described. For this reason, the mechanisms associated with this uncommon toxicities are still unknown.

Methods: This is a single-center prospective observational pilot study including cancer patients receiving PD-1/PD-L1 inhibitors alone or in combined treatment.
Inclusion Criteria: Patients that have a diagnosis of cancer undergoing treatment using anti-PD1 or anti-PD-L1 checkpoint inhibitors (melanoma, non small cell lung cancer, renal carcinoma etc.); 18 years of age or over; histologically confirmed cancer diagnosis; mandatory written informed consent.
Exclusion criteria: Patients or family refusal; patients with immunological and/or rheumatological pre-existing disease; patients on immunotherapic treatments.
Enrolled patients will be assessed before the treatment (T0) and after 3 (T1), 6 (T2) and 12 (T3) months, for rheumatic diseases development and/or ocular-releated IrAEs; patients will be also profiled for T helper subpopulations, cytokines/chemokines expression and related microRNAs alterations.

Expected outcomes: The main outcome expected from our study is to demonstrate a possible deregulation in the profile of immune cell populations as well as immune mediators at T0 and/or during the treatment of cancer patients with anti PD1/PD-L1, correlating it with IrAEs onset, the safety and the overall response rate to the treatments.