Thyroid Dysfunctions Due to Immune Checkpoint Inhibitors: A Review

Abstract

Aim: Immune checkpoint inhibitors are anti-cancer drugs associated with adverse events that result from releasing the immune system against self-antigens while attacking cancer cells. Thyroid dysfunctions are among the most common associated adverse events.

Materials and methods: We conducted a systematic search of the literature in 2 databases: PubMed and Medline. Articles that reported thyroid adverse events of immune checkpoint inhibitors were reviewed. Thyroid disorders include hyperthyroidism and hypothyroidism and are most commonly seen with programmed cell death protein 1 and programmed death-ligand 1 inhibitors.

Conclusions: Thyroid disorders are common side effects seen with check point inhibitors and are treated, depending on the clinical situation, by adequate hormonal replacement, thionamides, corticosteroids or observation only. The use of high dose corticosteroids has not been established as a treatment of thyroid toxicities. Thyroid function tests screening should be a part of baseline laboratory testing of all patients undergoing treatment with immune checkpoint inhibitors.

Keywords: anti-PD1; anti-PDL1; immune check point inhibitors; thyroid dysfunction.

Figure 1

CTLA-4 pathway: (A) T cell activation in response to the tumor-associated antigen requires 2 signals. The first signal is achieved when the major histocompatibility complex (MHC) on the surface of the antigen-presenting cell (APC) recognizes the T-cell receptor (TCR) of the T cell. The second signal is the binding of CD80/86 (also known as B7) on the APC cell with the CD28 receptor on the T cell. This will lead to the activation of the immune response against the tumor cells. (B) CTLA-4 (cytotoxic T-lymphocyte-associated antigen-4), a homolog of CD28, is a checkpoint present on T cells that limits proliferative response of activated T-cell by competing with CD28 for its ligand CD80/86. This inhibition will interrupt the second signal. (C) Monoclonal antibodies against CTLA-4 block CTLA-4 and will lead to T- cell activation and proliferation against the tumor cells.

Figure 2

PD-1- PD-L1 pathway: (A) PD-1 is a checkpoint present on the surface of T cells. When PD-1 binds to its ligands, PD-L1/2 present on APC and cancer cells, this will result in the inhibition of T cell activity in favour of tumor survival. (B) Monoclonal antibodies against PD-1 or PDL-1/2 will lead to the activation of the immune response against the tumor cells.