Expression of T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domains (TIGIT) in anaplastic thyroid carcinoma

Abstract

BackgroundImmune checkpoint proteins have not been fully examined in follicular cell-derived thyroid carcinoma and medullary thyroid carcinoma (MTC). Anaplastic thyroid carcinoma (ATC) is one of the most aggressive carcinomas. Even multimodal treatment does not result in favorable clinical outcomes for patients with ATC. Anti-tumor immunity has therefore been highlighted as having therapeutic promise for ATC.MethodsWe examined a novel immune checkpoint receptor, T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domains (TIGIT), in variable thyroid lesions: adenomatous goiter, follicular adenoma, and thyroid carcinoma (TC) using immunohistochemistry (IHC).ResultsOur IHC results showed that TIGIT expression was detected in cancer cells of MTC and high-grade TC: poorly differentiated thyroid carcinoma (PDTC) and ATC. Neoplastic cells were positive for TIGIT in four of five MTCs (80.0%), 17 of 31 ATCs (54.8%) and in 3 of 12 PDTCs (25.0%). TIGIT was not detected in any adenomatous goiters, thyroid benign tumors, or differentiated thyroid carcinoma (DTCs). Intriguingly, ATC cells showing pleomorphic/giant cell features were positive for TIGIT, while ATC cells with other cell morphologies lacked the immunoreactivity. Intra-tumoral immune cell was inclined to be enriched in TIGI-positive ATC. Although coexisting papillary thyroid carcinoma (PTC) components demonstrated high-grade microscopic features, neither the PTC nor follicular thyroid carcinoma (FTC) components expressed TIGT in any composite ATCs.ConclusionTIGIT was immunohistochemically found in MTC with high frequency and partially in high-grade TC. TIGIT expression in cancer cells may be beneficial for a potential utility in MTC and a subset of high-grade TC, especially ATC therapy.