p53 activation effect in the balance of T regulatory and effector cell subsets in patients with thyroid cancer and autoimmunity

Carcinomas evade the host immune system by negatively modulating CD4+ and CD8+ Teffector lymphocytes through forkhead box protein 3 (FOXP3) positive T regulatory cells’increased activity. Furthermore, interaction of the programmed cell death 1 (PD1)molecule and its ligand programmed cell death ligand 1 (PDL1) inhibits the antitumoractivity of PD1+ T lymphocytes. Immunotherapy has become a powerful strategy fortailored cancer patients’ treatment both in adult and pediatric patients aiming to generatepotent antitumor responses. Nevertheless, immunotherapies can generate autoimmuneresponses. This study aimed to investigate the potential effect of the transformationrelatedprotein 53 (p53) reactivation by a peptide-based inhibitor of the MDM2/MDM4heterodimer (Pep3) on the immune response in a solid cancer, i.e., thyroid carcinomafrequently presenting with thyroid autoimmunity. In peripheral blood mononuclear cell ofthyroid cancer patients, Pep3 treatment alters percentages of CD8+ and CD4+ Tregulatory and CD8+ and CD4+ T effector cells and favors an anticancer immuneresponse. Of note that reduced frequencies of activated CD8+ and CD4+ T effectorcells do not support autoimmunity progression. In evaluating PD1 expression under p53activation, a significant decrease of activated CD4+PD1+ cells was detected in thyroidcancer patients, suggesting a defective regulation in the initial activation stage, thereforegenerating a protective condition toward autoimmune progression.