Regulatory T cells (Tregs) are immunosuppressive immune cells that play an important role in tumor development. Suppression of Treg function is considered to be an effective strategy for cancer therapy. Glycoprotein A repetitions predominant (GARP) has been found on the surface of activated Tregs. GARP has been recently observed in only a few solid tumors including breast, colon, lung cancers, and melanoma. However, its function in cancers remains unknown. Here, we investigated the expression of GARP in human papillary thyroid carcinoma (PTC) and its prognostic significance. In this study, immunohistochemistry was performed to examine the expression of GARP and Foxp3 in 19 human PTC tissues (including 10 cases with and 9 cases without lymph node metastasis) and 20 benign thyroid diseases (including 10 cases with nodular goiter and 10 cases with adenoma). Compared with benign thyroid diseases, we found a significant increase in the expression of GARP in PTC. Increased GARP expression in PTC was positively correlated with increased expression of Foxp3, which is very important for development of Tregs. But, there is no significant association of elevated expression of GARP with lymph node metastasis in PTC. Our results indicate that GARP is implicated in the development of PTC and might be a potential novel target for anticancer therapy. In addition, our findings further support the existence of a positive-feedback loop between GARP and Foxp3.
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Article Synopsis
- TGF-β is a crucial protein involved in development and immunity, usually expressed in a latent form associated with its prodomain and presented on immune cells via GARP.
- Recent findings indicate that TGF-β can signal without needing to fully dissociate from its latent form, challenging existing beliefs.
- New research using advanced microscopy shows that the binding of integrin αvβ8 can alter the structure of latent TGF-β, allowing it to activate signaling pathways without being released, and this mechanism may apply to other similar receptor/ligand systems.
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