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The Role of Programmed Cell Death Ligand-1/ Programmed Cell Death-1 (PD-L1/PD-1) in HPV-induced Cervical Cancer and Potential for its Use in Blockade Therapy

Author(s):

Lifang Zhang, Yu Zhao, Quanmei Tu, Xiangyang Xue, Xueqiong Zhu and Kong-Nan Zhao*   Pages 1 - 16 ( 16 )

Abstract:


Background: Cervical cancer induced by infection with human papillomavirus (HPV) remains a leading cause of mortality for women worldwide although preventive vaccines and early diagnosis have reduced morbidity and mortality. Advanced cervical cancer can only be treated with either chemotherapy or radiotherapy but outcomes are poor. The median survival for advanced cervical cancer patients is only 16.8 months.

Methods: We undertook a structural search of peer-reviewed published studies based on 1). Characteristics of programmed cell death ligand-1/programmed cell death-1(PD-L1/PD-1) expression in cervical cancer and upstream regulatory signals of PD-L1/PD-1 expression, 2). The role of the PD-L1/PD-1 axis in cervical carcinogenesis induced by HPV infection and 3). Whether the PD-L1/PD-1 axis has emerged as a potential target for cervical cancer therapies.

Results: One hundred and twenty-six published papers were included in the review, demonstrating that expression of PD-L1/PD-1 is associated with HPV-caused cancer, especially with HPV 16 and 18 which account for approximately 70% of cervical cancer cases. HPV E5/E6/E7 oncogenes activate multiple signaling pathways including PI3K/AKT, MAPK, hypoxia-inducible factor 1α, STAT3/NF-kB and MicroRNAs, which regulate PD-L1/PD-1 axis to promote HPV-induced cervical carcinogenesis. The PD-L1/PD-1 axis plays a crucial role in immune escape of cervical cancer through inhibition of host immune response. creating an "immune-privileged" site for initial viral infection and subsequent adaptive immune resistance, which provides a rationale for therapeutic blockade of this axis in HPV-positive cancers. Currently, Phase I/II clinical trials evaluating the effects of PD-L1/PD-1 targeted therapies are in progress for cervical carcinoma, which provide an important opportunity for the application of anti-PD-L1/anti-PD-1 antibodies in cervical cancer treatment.

Conclusion: Recent research developments have led to an entirely new class of drugs using antibodies against the PD-L1/PD-1 thus promoting the body’s immune system to fight the cancer. The expression and roles of the PD-L1/ PD-1 axis in the progression of cervical cancer provide great potential for using PD-L1/PD-1 antibodies as a targeted cancer therapy.

Keywords:

Programmed cell death ligand-1(PD-L1), Programmed cell death-1(PD-1), Cervical cancer, Human papillomavirus, Immune cancer therapy, Vaccination

Affiliation:

School of Basic Medical Science, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, Department of obstetrics and Gynaecology, The second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, Zhejiang, Department of obstetrics and Gynaecology, The second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, Zhejiang, School of Basic Medical Science, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, Department of obstetrics and Gynaecology, The second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, Zhejiang, School of Basic Medical Science, Wenzhou Medical University, Wenzhou, 325035, Zhejiang



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