The effect of Wnt/β-catenin signaling on PD-1/PDL-1 axis in HPV-related cervical cancer

Abstract

Infection with high-risk human papillomavirus (HPV), including HPV-16 and HPV-18, is the main cause of malignancies, such as cervical cancer. Viral oncoproteins encoded by HPV are expressed in HPV-positive cancers and associated with the early cancer stages and the transformation of normal cells. The signaling pathways involved in the transformation of normal cells to cancerous form and the subsequently expressed programmed cell death-ligand 1 (PD-L1) on the surface of the transformed cells lead to a disruption in recognition of tumor cells by the immune cell system, including T lymphocytes and dendritic cells which lead to the development of cervical cancer malignancy.These cells also produce modest levels of cytokines during exhaustion, tumor-infiltrating T CD4+ cells with high levels of PD-1 and CD39 release considerable quantities of cytokines. The Wnt/β-catenin signaling pathway, which controls the expression of genes involved in the tumor cells' markers, is demonstrated to be one of the most potent cancer stimulants. It leads to the evasion of the tumor cells from immune cell detection and ultimately avoids being recognized by dendritic cells or T-cells. PD-L1, as an inhibitory immune checkpoint, is essential for controlling immune system activity by inhibiting T-cells' inflammatory function. In the present review, we looked into how Wnt/β-catenin affects the expression of PD-L1 and related genes like c-MYC in cancer cells and its role in the development of HPV-induced malignancy. We hypothesized that blocking these pathways could be a potential immunotherapy and cancer prevention method. Abbreviation List APCs Antigens presenting cells APC Adenomatous polyposis coli SATB1 AT-rich sequence binding protein-1 β-TrCP Beta-transducing repeat-containing protein Brg-1 Brahma-related gene 1 CD Cluster of differentiation c-MYC Cellular myelocytomatosis CIN Cervical intraepithelial neoplasia CREPT Cell cycle-related and expression elevated protein in tumor CBP/p300 CREB-binding protein CK1 Casein kinase 1

Baicalein targets STMN1 to inhibit the progression of nasopharyngeal carcinoma via regulating the Wnt/β‐catenin pathway

“…45 The Wnt/β-catenin pathway also played the vital roles in human papilloma virus (HPV)-related cervical cancer and triple-negative breast cancer. 46,47 Furthermore, the Wnt/β-catenin signaling pathway modulated by the miR-506/LHX2 axis was involved in regulating nasopharyngeal carcinoma tumor growth and metastasis. 48 In the present study, we found that STMN1 knockdown could inactivate the Wnt/β-catenin signaling pathway in nasopharyngeal carcinoma cells, which was blocked by SKL2001, an agonist of the Wnt/β-catenin pathway.…”

“…In endometrial cancer, KIF15 depletion markedly repressed epithelial–mesenchymal transition (EMT) and stemness via regulating the Wnt/β‐catenin pathway 45 . The Wnt/β‐catenin pathway also played the vital roles in human papilloma virus (HPV)‐related cervical cancer and triple‐negative breast cancer 46,47 . Furthermore, the Wnt/β‐catenin signaling pathway modulated by the miR‐506/LHX2 axis was involved in regulating nasopharyngeal carcinoma tumor growth and metastasis 48 .…”

Editorial: Dual role of inflammatory mediators in cancer immunotherapy

“…The findings suggest that PD-1 plays a central role in suppressing Tc17 differentiation and its plasticity in relation to cytotoxic Tc1 cells driven tumor rejection, making it an efficient therapeutic target for inducing tumor rejection. This mechanism further expands our thinking to develop more related treatment strategies based on PD-1 and PD-L1 ( 7 ).…”

Advancing Immunotherapies for HPV-Related Cancers: Exploring Novel Vaccine Strategies and the Influence of Tumor Microenvironment

“…It is no different, therefore, that such knowledge also applies to HPV-related cancer. These studies make use of antigens specific to HPV, such as the E6 and E7 oncogenes [ 56 , 57 , 58 , 59 ], the immune checkpoints molecules such as the protein programmed cell death protein 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1) [ 60 ], to whole cell therapies [ 61 , 62 ]. However, further studies are needed to understand and design immunotherapies against HPV-related cancers.…”