Open Access

REVIEW

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

by PARISA SHIRI AGHBASH^1,2,4, NIMA HEMMAT¹, BEHZAD BARADARAN^1,3, AHAD MOKHTARZADEH¹, VAHDAT POORTAHMASEBI^2,4, MAHIN AHANGAR OSKUEE^2,4, HOSSEIN BANNAZADEH BAGHI^1,2,4,*

1 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, 5165665931, Iran
2 Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, 5165665931, Iran
3 Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, 5165665931, Iran
4 Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, 5165665931, Iran

* Corresponding Author: HOSSEIN BANNAZADEH BAGHI. Email:

Oncology Research 2022, 30(3), 99-116. https://doi.org/10.32604/or.2022.026776

Received 25 September 2022; Accepted 28 December 2022; Issue published 12 January 2023

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.

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