Evaluation of the Expression of PD-L1, CTLA-4, and LAG-3 in Human Thyroid Carcinoma

  • Background: Most thyroid carcinomas are indolent and have a favorable prognosis. However, ATC and PDTC are two rare, aggressive, and lethal subtypes of thyroid carcinoma with a poor prognosis. Novel treatment strategies are essential for successful therapy of these aggressive thyroid malignancies. Cancer immunotherapy and the use of immune checkpoint inhibitors are rapidly advancing and considered to be potent therapeutic strategies for especially aggressive cancers. We hypothesized that thyroid carcinoma overexpress some immune checkpoints and ligands and could therefore respond to novel immunotherapies. Methods: In this study, 105 thyroid tissues, including 17 normal thyroids, 14 benign thyroids, 19 PTC, 13 FTC, 23 PDTC, and 19 ATC, were selected for H&E staining and immunohistochemical analysis of the immune checkpoint proteins PD-L1, CTLA-4, and LAG-3. Results: The expression levels of PD-L1, CTLA-4, and LAG-3 were significantly higher in thyroid malignant tissues, compared to benign and normal thyroid tissues. In addition, the positive expression rates of PD-L1, CTLA-4, and LAG-3 were higher in ATC than DTC or PDTC. Additionally, there was a significant correlation between the number of CTLA-4+ and LAG-3+ particles in thyroid carcinoma. Conclusion: Our results show that PD-L1, CTLA-4, and LAG-3 are potential targets for aggressive thyroid malignant tumor immunotherapy and suggest that combination of CTLA-4 and LAG-3 immune checkpoint inhibitors might be an attractive strategy for thyroid carcinoma patients with dual positive expression of these proteins.

 

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