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p53 Activation Effect in the Balance of T Regulatory and Effector Cell Subsets in Patients With Thyroid Cancer and

Andrea Arena1, Antonio Stigliano2, Eugenia Belcastro1

  • 1Infectivology and Clinical Trials Research Department, Children's Hospital Bambino Gesù, Rome, Italy.

Frontiers in Immunology
|September 20, 2021
PubMed

Insights

Reactivating p53 with Pep3 peptide inhibitor in thyroid cancer patients enhances anticancer immune responses. This approach modulates T cell populations and reduces T cell activation, potentially preventing autoimmune side effects common with immunotherapies.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Carcinomas employ mechanisms like regulatory T cells (FOXP3+) and PD1/PDL1 interactions to suppress anti-tumor immunity.
  • Cancer immunotherapies, while potent, carry the risk of inducing autoimmune adverse events.
  • Thyroid carcinoma often co-exists with thyroid autoimmunity, complicating treatment strategies.

Purpose of the Study:

  • To investigate the impact of p53 reactivation using the MDM2/MDM4 inhibitor Pep3 on the immune response in thyroid carcinoma.
  • To assess Pep3's effect on T cell populations and immune modulation in the context of cancer and autoimmunity.
  • To evaluate programmed cell death 1 (PD1) expression following p53 activation to understand its role in immune regulation.

Main Methods:

  • Treatment of peripheral blood mononuclear cells (PBMCs) from thyroid cancer patients with Pep3.
  • Analysis of T cell subsets, including CD4+ and CD8+ T effector and T regulatory cells.
  • Quantification of programmed cell death 1 (PD1) expression on activated T cells.

Main Results:

  • Pep3 treatment altered the percentages of CD4+ and CD8+ T effector and T regulatory cells in thyroid cancer patients.
  • The treatment promoted an anti-cancer immune response by favorably modulating T cell populations.
  • Reduced frequencies of activated CD4+ and CD8+ T effector cells were observed, suggesting a mechanism to mitigate autoimmunity.
  • A significant decrease in activated CD4+PD1+ cells was detected, indicating a potential protective effect against autoimmune progression.

Conclusions:

  • Reactivation of p53 via Pep3 can modulate immune responses in thyroid carcinoma.
  • Pep3 treatment favors an anti-cancer immune response while potentially suppressing autoimmunity.
  • The observed reduction in activated CD4+PD1+ cells suggests a protective role against autoimmune complications in cancer immunotherapy.
Keywords:
T effector cellsT regulatory cellsimmunotherapyp53pediatric diseasethyroid cancerthyroiditis

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