Increased expression of PD-L1 by the human papillomavirus 16 E7 oncoprotein inhibits anticancer immunity

Liu, Chaoqi; Lu, Jiao; Tian, Huiqun; Du, Yong; Zhang, Lin; Feng, Jing; Ding, Yuan; Li, Zhiying

doi:10.3892/mmr.2016.6073

Cited by 21 publications

(22 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hypermethylation of Rad51B was shown in all three cancers to correlate with increased expression of both CTLA-4 and PD-L1 and hypermethylation of XRCC3 (also involved in homologous recombination) correlated with increased CTLA-4 expression in all three cancers [87]. The HPV E7 protein itself has also been shown to drive PD-L1 expression [88]. In addition, recent evidence has shown that E6 and E7 can lead to hypermethylation and silencing of various immune genes, such as type 1 interferons, HLA-E and CXCL14 [89].…”

Section: Pre-clinical Evidence Of Differences Between Human Papillomamentioning

confidence: 86%

The Human Papillomavirus as a Common Pathogen in Oropharyngeal, Anal and Cervical Cancers

et al. 2019

View full text Add to dashboard Cite

The burden of human papillomavirus (HPV)-related cancers worldwide is significant. Although the incidence of cervical cancer is decreasing due to cervical screening programmes, the incidences of oropharyngeal, anal and vulval cancers are increasing. The introduction of HPV vaccination programmes in many countries has had an impact on HPV infection rates but due to the time-lag from initial HPV infection to the development of invasive carcinoma, the impact on the incidence of HPV-related cancer will take more time to become evident. This review explores the common aspects of HPV-related cancers and how they differ from their HPV-negative counterparts, both clinically and molecularly. It also covers the implications this has on future treatment strategies, including the possible role of immunotherapy.

show abstract

Section: Pre-clinical Evidence Of Differences Between Human Papillomamentioning

confidence: 86%

The Human Papillomavirus as a Common Pathogen in Oropharyngeal, Anal and Cervical Cancers

et al. 2019

View full text Add to dashboard Cite

show abstract

“…In HPV-associated oropharyngeal squamous cell carcinoma, antigen-specific CD8 + T-cell infiltration into tumor is highly correlative with positive patient outcomes [33]. CD8 + T-cell functions are limited by either E7-mediated expression of suppressors such as PD-L1 or by low levels of antigen presentation [34,35]. To overcome this T-cell tolerance, several immunotherapies have been tested and approved by the FDA [36].…”

Section: Discussionmentioning

confidence: 99%

CXCL14 suppresses human papillomavirus-associated head and neck cancer through antigen-specific CD8+ T-cell responses by upregulating MHC-I expression

et al. 2019

View full text Add to dashboard Cite

Evasion of the host immune responses is critical for both persistent human papillomavirus (HPV) infection and associated cancer progression. We have previously shown that expression of the homeostatic chemokine CXCL14 is significantly downregulated by the HPV oncoprotein E7 during cancer progression. Restoration of CXCL14 expression in HPV-positive head and neck cancer (HNC) cells dramatically suppresses tumor growth and increases survival through an immunedependent mechanism in mice. Although CXCL14 recruits natural killer (NK) and T cells to the tumor microenvironment, the mechanism by which CXCL14 mediates tumor suppression through NK and/or T cells remained undefined. Here we report that CD8 + T cells are required for CXCL14-mediated tumor suppression. Using a CD8 + T-cell receptor transgenic model, we show that the CXCL14-mediated antitumor CD8 + T-cell responses require antigen specificity. Interestingly, CXCL14 expression restores major histocompatibility complex class I (MHC-I) expression on HPV-positive HNC cells downregulated by HPV, and knockdown of MHC-I expression in HNC cells results in loss of tumor suppression even with CXCL14 expression. These results suggest that CXCL14 enacts antitumor immunity through restoration of MHC-I expression on tumor cells and promoting antigen-specific CD8 + T-cell responses to suppress HPV-positive HNC.

show abstract

“…[ 3 – 4 ] Cervical cancer as a tumor had the most closely relation to HPV infection, the previous studies revealed that PD-L1 was a solid biomarker of productive HPV infection in the cervix, [ 5 ] and the overexpress of HPV16 E7 oncoprotein in the cervical epithelial carcinoma increased the expression level of the PD-L1 protein. [ 6 ] But all the reports first ignored the difference of PD-L1 between only HPV infection but cervical normal patients and HPV infection with cervical lesion patients; meanwhile, the samples of these studies were tissue specimens, neglecting the important of cervical exfoliated cells sample in cervical cell lesion study. At last, the previous studies did not include the relation between the specific HPV infection status and PD-L1 expression.…”

Section: Introductionmentioning

confidence: 99%

Association between PD-L1 and HPV status and the prognostic value for HPV treatment in premalignant cervical lesion patients

et al. 2017

View full text Add to dashboard Cite

The difference of PD-L1 expression between only HPV-positive patients and premalignant cervical lesion patients did not be reported in present studies. And to test the PD-L1 expression in some cervical cell lesion studies using cervical exfoliated cells sample also was ignored. Meanwhile, the PD-L1 expression as a predictive biomarker still existed controversy. So in the study, first to compare the expression of PD-L1 between only HPV-positive patients and premalignant cervical lesion patients, then to research the association between PD-L1 and HPV status, lastly to explore the possible prognostic value for HPV treatment in premalignant cervical lesion patients.Cervical exfoliated cells samples of 54 premalignant cervical lesion patients with HPV16 infection were collected; meanwhile the cervical exfoliated cells samples from 20 healthy women without HPV infection and 20 patients with only HPV16 infection but cervical cytology normal were collected as 2 control groups. Flow-through hybridization and gene chip (FHGC) was used to detect the HPV type, the PD-L1 expression was tested by Flow cytometry analysis, the methylation-sensitive high-resolution melting (MS-HRM) was used to test the HPV16 L1 gene methylation. The 54 premalignant cervical lesion patients were followed up in 18 months to assess the prognostic value of PD-L1 for HPV treatment.The PD-L1 positive cell rate and mean fluorescence intensity of PD-L1 positive cell in premalignant cervical lesion patients with HPV16 infection were higher than 2 control groups. Mean fluorescence intensity of PD-L1 positive cell were increased in 54 cases when existing multiple HPV status and high HPV16-L1 gene methylation (L1 gene methylation more than 50%). High PD-L1 expression (PD-L1 positive cell rate more than 10%), high HPV16-L1 gene methylation, and multiple HPV infection status could prolong the time to clean HPV infection by Kaplan–Meier analysis. Multivariate Cox proportional hazards analysis also showed that all of high PD-L1 expression, high HPV-L1 methylation, and multiple HPV infection status should increase the risk of HPV unclearance in premalignant cervical lesion patients; the hazard ratio (HR) was 2.043 (CI: 1.050–3.973), 2.797 (CI: 1.277–6.122), and 3.050 (CI: 1.406–6.615).PD-L1 expression only was correction with HPV infection when the infection induced the cervical cells to create the lesion. PD-L1 was the risk factor of HPV unclearance in premalignant cervical lesion patients, so anti-PD-L1 therapy could be a potential effectiveness way of HPV infection in premalignant cervical lesion patients.

show abstract

Increased expression of PD-L1 by the human papillomavirus 16 E7 oncoprotein inhibits anticancer immunity

Cited by 21 publications

References 10 publications

The Human Papillomavirus as a Common Pathogen in Oropharyngeal, Anal and Cervical Cancers

The Human Papillomavirus as a Common Pathogen in Oropharyngeal, Anal and Cervical Cancers

CXCL14 suppresses human papillomavirus-associated head and neck cancer through antigen-specific CD8+ T-cell responses by upregulating MHC-I expression

Association between PD-L1 and HPV status and the prognostic value for HPV treatment in premalignant cervical lesion patients

Contact Info

Product

Resources

About