The Immune Landscape of Papillary Thyroid Cancer in the Context of Autoimmune Thyroiditis

Pani F.

Writing - Original Draft Preparation

;Caria P.

Writing - Review & Editing

;Yasuda Y.;Makoto M.;Mariotti S.

Writing - Review & Editing

;Leenhardt L.;Roshanmehr S.;Caturegli P.;Buffet C.

2022-01-01

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Abstract

Simple Summary The association between papillary thyroid cancer and Hashimoto's thyroiditis went through a long-standing human debate recently elucidated by the establishment of a novel mouse model. Papillary thyroid carcinoma is an excellent model for studying the tumor immune microenvironment because it is naturally accompanied by immune cells, making it a good candidate for the treatment with immune checkpoint inhibitors. Papillary thyroid cancer (PTC) often co-occurs with Hashimoto's thyroiditis, an association that has long been reported in clinical studies, remaining controversial. Experimental evidence has recently shown that pre-existing thyroiditis has a beneficial effect on PTC growth and progression by a distinctive expansion of effector memory CD8 T cells. Although the link between inflammation and PTC might involve different components of the immune system, a deep characterization of them which includes T cells, B cells and tertiary lymphoid structures, Mye-loid cells, Neutrophils, NK cells and dendritic cells will be desirable. The present review article considers the role of the adaptive and innate immune response surrounding PTC in the context of Hashimoto's thyroiditis. This review will focus on the current knowledge by in vivo and in vitro studies specifically performed on animals' models; thyroid cancer cells and human samples including (i) the dual role of tumor-infiltrating lymphocytes; (ii) the emerging role of B cells and tertiary lymphoid structures; (iii) the role of myeloid cells, dendritic cells, and natural killer cells; (iv) the current knowledge of the molecular biomarkers implicated in the complex link between thyroiditis and PTC and the potential implication of cancer immunotherapy in PTC patients in the context of thyroiditis.