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Immune Checkpoint Protein Expression Defines the Prognosis of Advanced Thyroid Carcinoma
Yi Luo1,2, Yi-Chen Yang1,2, Cen-Kai Shen1,2
1Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
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.
Insights
Immune checkpoint inhibitors show promise for advanced thyroid cancer. High expression of certain immune checkpoints like PD-L1, VISTA, B7-H3, TIM3, and TIGIT correlates with poor prognosis in anaplastic, poorly differentiated, and papillary thyroid carcinoma.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Advanced thyroid carcinoma (TC), including anaplastic (ATC), poorly differentiated (PDTC), and locally advanced papillary (PTC), presents a poor prognosis.
- Novel therapeutic strategies are urgently needed for these aggressive TC subtypes.
- Immune checkpoint (ICP) inhibitors have shown potential, but their efficacy in advanced TC remains under investigation.
Purpose of the Study:
- To elucidate ICP expression profiles in advanced TC subtypes.
- To investigate the clinical significance and prognostic value of ICPs in ATC, PDTC, and advanced PTC.
- To explore the potential of ICP-targeted therapies for advanced TC.
Main Methods:
- Analysis of 234 TC patients, including 22 ATC, 44 PDTC, and 168 PTC (58 advanced).
- Immunohistochemistry on tissue microarrays (TMAs) to assess the expression of 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).
- Correlation analysis between ICP expression and clinical outcomes.
Main Results:
- Anaplastic thyroid carcinoma (ATC) exhibited the highest ICP positive rates and co-expression.
- High PDL1 expression in ATC correlated with a poor prognosis.
- In poorly differentiated thyroid carcinoma (PDTC), shorter survival was associated with VISTA, B7H3, TIM3, and TIGIT expression, with greater co-expression leading to poorer outcomes.
- VISTA and B7H3 were frequently expressed in advanced papillary thyroid carcinoma (PTC) and linked to poor prognosis.
Conclusions:
- PDL1 expression is associated with overall survival in ATC.
- A subset of PDTC patients with poor prognosis may be immunogenic, characterized by co-expression of VISTA, B7H3, TIM3, and TIGIT.
- VISTA and B7H3 serve as prognostic biomarkers in advanced PTC.
- Targeting these ICPs, individually or in combination, could offer future therapeutic avenues for advanced TCs.
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