Thyroid hormone, PD-L1, and cancer

Abstract

Objective: Thyroid hormone plays a vital role in maintaining whole-body physiological activities. However, several different disorders can arise when thyroid hormone is abnormal. Even more, thyroid hormone has been shown to stimulate cancer cell proliferation at physiological concentration. By binding to cell surface integrin αvβ3, thyroid hormone, especially thyroxine activates ERK1/2 activation and sequentially stimulates cell proliferation. Different mechanisms have been demonstrated to be involved in thyroxine-induced cancer proliferation. Checkpoint, PD-1/PD-L1, has shown highly correlated to cancer proliferation and survival. Data Sources: We examined actions of thyroxine and Nano-diamino-tetrac (NDAT; Nanotetrac) on PD-L1 mRNA abundance (qPCR) and PD-L1 protein content in various cancer cells. Methodologies used are qPCR, Western blot analyses, confocal microscopy, and xenograft. Study Selection: We investigate mechanisms involved in thyroid hormone-induced PD-L1 expression and inhibitory effect of NDAT on thyroid hormone-induced PD-L1 expression. Either blocking thyroid hormone-binding on integrin αvβ3 or using NDAT can inhibit PD-L1 expression. Results: Our studies indicate that thyroid hormone induces PD-L1 expression via activating ERK1/2, PI3K, and STAT3 in different types of cancer cells. NDAT inhibits the cancer cell PI3-K and MAPK signal transduction pathways that are critical to PD-L1 gene expression. Other studies on PubMed also indicate thyroxine's actions are via integrin αvβ3. Conclusions: Thyroid hormone-induced PD-L1 expression not only facilitates cancer cell proliferation but also interferes with chemotherapy. In this current review, we will discuss mechanisms involved in thyroid hormone-induced PD-L1 expression. In addition, role of PD-L1 in thyroid hormone-induced cancer growth and metastasis will be addressed.