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

Abstract

Background Immune 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. Methods We 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). Results Our 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. Conclusion TIGIT 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.

TIGIT in Lung Cancer: Potential Theranostic Implications

“…These findings justify and explain the success of TIGIT immunotherapy in PD-L1+ non-small cell lung carcinoma [11,38]. TIGIT expression was also documented on tumor cells, especially in cutaneous melanoma [39], choroidal melanoma [40], thyroid cancer [41], undifferentiated pleomorphic sarcoma [42], lung adenocarcinoma [43], and esophageal cancer [44]. An interesting study has also demonstrated TIGIT expression on CD20+ TILs in gastric cancer [45], where cases with higher TIGIT+CD20+ infiltrates exhibited a worse prognosis.…”

CTHRC1 promotes anaplastic thyroid cancer progression by upregulating the proliferation, migration, and invasion of tumor cells

“…Endogenous peroxidase was removed using 3% hydrogen peroxide, and the sections were then blocked with goat serum before being incubated with primary antibodies, including anti-CTHRC1 (1:500, ab256458; Abcam, UK), anti-E-Cadherin (1:100, ab235682; Abcam, Cambridge, UK), anti-Vimentin (1:200, #5741; Cell Signaling Technology, Danvers, MA, USA), anti-Snail (1:50, A5243; ABclonal Science Inc., Woburn, MA, USA) overnight at 4 °C. The sections were then incubated with a secondary antibody for 1 h at 25 °C, followed by color development using diaminobenzidine (DAB), counterstaining with hematoxylin, differentiation with hydrochloric acid ethanol, dehydration using an ethanol gradient, the sections were cleared in xylene and imaged ( Nakazawa et al, 2022 ). All immunohistochemical stainings were evaluated blindly and independently by two investigators.…”