<p>HIF1α/PD-L1 axis mediates hypoxia-induced cell apoptosis and tumor progression in follicular thyroid carcinoma</p>

Abstract

Background Hypoxia-inducible factor 1α (HIF-1α) and programmed cell death-1 protein ligand 1 (PD-L1) are implicated in the metastasis and progression processes of multiple cancers. Hypoxia selectively elevates PD-L1 expression via HIF1α activation in several solid tumors; however, the regulatory effect of HIF1α on PD-L1 in the pathogenesis of follicular thyroid cancer (FTC) remains unclear. This study aims to investigate the regulatory effect of HIF1α on PD-L1 and their potential roles in FTC pathogenesis. Methods Spearman correlation analysis was performed to clarify the relationships between HIF1α and PD-L1 expressions and the clinicopathologic characteristics. The expressions of HIF1α and PD-L1 at mRNA and protein levels were analyzed by qRT-PCR and Western blot. Hypoxia induction and cell transfection were conducted in FTC cells. TUNEL and Annexin V staining were used to detect the cell apoptosis. FTC xenograft tumor models were generated to evaluate the roles of HIF1α and PD-L1 in vivo. Results Here, we found that the expressions of HIF1α and PD-L1 were significantly increased in FTC tissues and were correlated with the FTC clinicopathologic features, such as the tumor size, T stage, TNM staging, and metastasis. In FTC cells, hypoxia-induced increased HIF1α and PD-L1 expression. Knockdown of HIF1α inhibits hypoxia-induced PD-L1 expression and cells apoptosis. Moreover, inhibition of HIF1α or PD-L1 significantly delays tumor growth and metastasis in vivo. Conclusion Hypoxia could promote FTC progression by upregulating HIF1α and PD-L1, which could serve as the molecular targets for FTC treatment.

The Extrinsic and Intrinsic Roles of PD-L1 and Its Receptor PD-1: Implications for Immunotherapy Treatment

“…Additionally, some cytokines have been shown to work synergistically to upregulate PD-L1 expression in tumors such as TNFα with IFNγ (166) and with IL-17 (162). Besides inflammatory cytokines extrinsically modulating PD-L1 expression, hypoxia in the tumor microenvironment selectively elevates PD-L1 expression via HIF-1α activation in melanoma, breast, lung, thyroid and prostate cancer (9, 146,167). In recent studies, HIF-2α has also been shown to correlate with PD-L1 expression in clear cell renal cell carcinoma (168,169).…”

From biomarkers to therapeutic targets: the promise of PD-L1 in thyroid autoimmunity and cancer

“…Of clinical relevance, the overexpression of PD-L1 appears to predict worse prognosis, identifying patients at-risk of TC progression, representing real hope for the early management of advanced WDTC (18 clinical studies totaling 3107 patients, Table 3 ) 34 - 37 , 48 - 50 , 57 , 61 - 70 . Indeed, the expression of PD-L1 independently correlated with all clinicopathological markers of poor TC prognosis 5 : such as male gender, an age > 45 years 49 , 50 , 69 , tumor size (including extra-thyroid or multifocal lesions) 36 , 49 , 57 , 63 , 66 , 69 , lymphovascular invasion and lymph node metastasis 34 , 36 , 49 , 62 , 64 , 65 , 69 , 70 , or TNM stage 48 , 50 , 63 . Not surprisingly given its role in tumor immune escape, PD-L1 overexpression (protein and mRNA) is associated with reduced progression-free survival (PFS) in PTC patients 48 , 49 , 57 , 64 , 69 .…”

<p>miR-31 Modulates Liver Cancer HepG2 Cell Apoptosis and Invasion via ROCK1/F-Actin Pathways</p>

“…A one-step TUNEL kit (Beyotime Institute of Biotechnology, Haimen, China) was used for TUNEL staining as previously described. 28 After the treatment, HepG2 cells were incubated with fluorescein-dUTP (Invitrogen; Thermo Fisher Scientific, Inc.) to stain apoptotic cell nuclei and DAPI (5mg/mL) to stain all cell nuclei at room temperature for 3 min. The slides were imaged under a confocal microscope at least 5 random separate fields.…”