Although the mutational burden of thyroid cancer is relatively low in comparison to others, defining this tumor as “cold” [15], immunotherapy is considered a novel therapeutic approach, and it has been recently taken into consideration for less differentiated forms of thyroid carcinoma or in those tumors that develop RAI refractoriness, also in association with other drugs such as MAPK inhibitors, PI3K/Akt, other multi-kinase inhibitors (TKI) or other chemotherapy adjuvants, including metformin-modified chitosan (Ch-Met), which could modulate the expression of PD-L1 [15,16,17]. This evidence concerns the gene CD274 and neoplasm.