p53 activation 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+ T effector lymphocytes through forkhead boxprotein 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 antitumor activity of PD1+ T lymphocytes.Immunotherapy has become a powerful strategy for tailored cancer patients' treatment both in adult and pediatric patientsaiming to generate potent antitumor responses. Nevertheless, immunotherapies can generate autoimmune responses. This studyaimed to investigate the potential effect of the transformation-related protein 53 (p53) reactivation by a peptide-based inhibitorof the MDM2/MDM4 heterodimer (Pep3) on the immune response in a solid cancer, i.e. thyroid carcinoma frequently presentingwith thyroid autoimmunity. In peripheral blood mononuclear cell of thyroid cancer patients, Pep3 treatment alters percentages ofCD8+ and CD4+ T regulatory, CD8+ and CD4+ T effector cells and favours an anticancer immune response. Of note that reducedfrequencies of activated CD8+ and CD4+ T effector cells do not support autoimmunity progression. In evaluating PD1 expressionunder p53 activation, a significant decrease of activated CD4+PD1+ cells was detected in thyroid cancer patients, suggesting adefective regulation in the initial activation stage, therefore, generating a protective condition toward autoimmune progression.