Which theory is most plausible in your opinion regarding the cause of thyroiditis after immunotherapy?
the NK and monocyte increasing after use of anti PD-1 Ab
or the blockade of peripheral tolerance inside the thyroid because the thyroid tissue highly expresses the PD-L1.
Hello Kaled Nather Taha
Immune Checkpoint Inhibitors (ICIs) enhance anti-tumour responses. ICIs may prompt the immune system to attack healthy organs causing adverse changes in the skin, GI tract and endocrine system. Thyroid dysfunction is a common endocrine side effect. The administration of ICIs may trigger T
cell-mediated pathways that induce subsequent thyroid dysfunction. PD-1 or PDL-1 blockage is likely to trigger pre-existing CD8+ T cell activation. For thyroiditis, the effect of anti-PD-1 and anti-PDL-1 agents could be more than anti-CTLA-4 agents.
Treg plays a role in the inhibitory effect through cell-cell contact and secreting a regulatory cytokine IL-10. The decrease of IL-10 may be related to increase in TPO antibody suggesting loss of Treg energy and development of thyroid irAEs. Studies have shown that CD4+ Th1 which express IFN gamma and IL-2 is increased and there is a decrease in G-CSF after anti-PD-1 treatment. G-CSF has a strong positive correlation with Th2 cytokine and could cause a decrease in Th2 cytokine activation indicating increased Th1 dominance in thyroid irAEs.
Whether NK cells and monocytes are involved in thyroid irAEs needs further investigation.
Best,
Dear Kaled Nather Taha , I believe both the circulating (NK, CD56, CD16) and the local anti-PD-L1/2 efficacy is a valid mechanism. There is a third additional possibly synergistic theory of a preexisting inflammation of the thyroid, since several cases have been reported of patients with a pre-existing Hashimoto's disease and subclinical hypothyroidism treated with ICI.
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