Immune Checkpoint Protein Expression Defines the Prognosis of Advanced Thyroid Carcinoma

Abstract

Background: Patients with advanced thyroid carcinoma (TC), such as anaplastic thyroid carcinoma (ATC), poorly differentiated thyroid carcinoma (PDTC), and locally advanced papillary thyroid carcinoma (PTC), have poor prognoses and require novel treatments. Immune checkpoint (ICP) inhibitors have demonstrated encouraging and good results; nevertheless, their effect in advanced TCs remains largely unclear. Thus, we demonstrated ICP profiles and investigated their potential clinical significance.

Methods: A total of 234 TC patients were involved, with 22 ATCs, 44 PDTCs, and 168 PTCs, including 58 advanced PTCs. Immunohistochemistry was performed to evaluate nine ICPs [programmed cell death ligand 1 (PDL1), Programmed cell death 1 (PD1), cytotoxic T lymphocyte-associated protein 4 (CTLA4), B and T lymphocyte attenuator (BTLA), T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), lymphocyte activation gene 3 (LAG3), V-domain immunoglobulin suppressor of T-cell activation (VISTA), B7 homolog 3 (B7-H3), and T-cell immunoglobulin and mucin domain- 3 protein (TIM3)] expression via tissue microarrays (TMAs), and clinical correlations were analyzed simultaneously.

Results: ATC had the highest positive rate of ICPs among the three pathological types, as well as relatively high ICP co-expression. ATC with high expression of PDL1 positivity had a poor prognosis. Shorter survival was associated with VISTA, B7H3, TIM3, and TIGIT expression in PDTC. The greater the co-expression of these four ICPs, the poorer the prognosis in PDTC patients. VISTA and B7H3 were the two most commonly expressed ICPs in advanced PTC, both of which were linked to a poor prognosis.

Conclusions: PDL1 is linked to the overall survival (OS) of ATC. A subset of PDTC is likely immunogenic with poor prognosis and co-expression of VISTA, B7H3, TIM3, and TIGIT. Furthermore, VISTA and B7H3 are prognostic biomarkers in advanced PTC. Single or combined blockade targeting these ICPs might be effective for advanced TCs in the future.

Keywords: anaplastic thyroid carcinoma; immune checkpoint; immunotherapy; locally advanced papillary thyroid carcinoma; poorly differentiated thyroid carcinoma.