The immune checkpoints CTLA-4 and PD-L1 in carcinomas of the uterine cervix

Karpathiou, Georgia; Chauleur, Céline; Mobarki, Mousa; Péoc’h, Michel

doi:10.1016/j.prp.2019.152782

Cited by 31 publications

(35 citation statements)

References 27 publications

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“…Zhao et al ( 6 ) found that MMP1 may be a novel biomarker for immunotherapy and prognostic assessment of patients with CC. Karpathiou et al ( 7 ) indicated that PD-L1 and CTLA-4 immune cell expression was associated with lymph node metastasis and are, therefore, potential therapeutic targets in CC. Wang et al ( 8 ) found that immune system-related genes referred to the T cell receptor (TCR) signaling pathway are associated with the overall survival (OS) of CSCC patients.…”

Section: Introductionmentioning

confidence: 99%

A novel prognostic prediction model based on seven immune-related RNAs for predicting overall survival of patients in early cervical squamous cell carcinoma

Qin

Cao

et al. 2021

BMC Med Genomics

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Background In this study, we aimed to mine immune-related RNAs expressed in early cervical squamous cell carcinoma to construct prognostic prediction models. Methods The RNA sequencing data of 309 cervical squamous cell carcinoma (CSCC) cases, including data of individuals with available clinical information, were obtained from The Cancer Genome Atlas (TCGA) database. We included 181 early-stage CSCC tumor samples with clinical survival and prognosis information (training dataset). Then, we downloaded the GSE44001 gene expression profile data from the National Center for Biotechnology Information Gene Expression Omnibus (validation dataset). Gene ontology annotation and the Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to analyze the biological functions of differentially expressed immune-related genes (DEIRGs). We established protein–protein interactions and competing endogenous RNA networks using Cytoscape. Using the Kaplan–Meier method, we evaluated the association between the high- and low-risk groups and the actual survival and prognosis information. Our univariate and multivariate Cox regression analyses screened for independent prognostic factors. Results We identified seven prognosis-related signature genes (RBAKDN, CXCL2, ZAP70, CLEC2D, CD27, KLRB1, VCAM1), the expression of which was markedly associated with overall survival (OS) in CSCC patients. Also, the risk score of the seven-gene signature discripted superior ability to categorize CSCC patients into high-risk and low-risk groups, with a observablydifferent OS in the training and validation datasets. We screened two independent prognostic factors (Pathologic N and prognostic score model status) that correlated significantly by univariate and multivariate Cox regression analyses in the TCGA dataset. To further explore the potential mechanism of immune-related genes, we observed associated essential high-risk genes with a cytokine–cytokine receptor interaction. Conclusions This study established an immune-related RNA signature, which provided a reliable prognostic tool and may be of great significance for determining immune-related biomarkers in CSCC.

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Section: Introductionmentioning

confidence: 99%

A novel prognostic prediction model based on seven immune-related RNAs for predicting overall survival of patients in early cervical squamous cell carcinoma

Qin

Cao

et al. 2021

BMC Med Genomics

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“…Moreover, PD-L1 expression is associated with an advanced grade of cancer, presence of metastasis, poor prognosis, resistance to chemotherapy, and increased mortality [ 15 , 18 – 25 ]. Karpathiou et al found that immune cell and tissue expression of PD-L1 were higher in SCC patients with lymph node metastasis and that the overexpression of PD-L1 is associated with a poor prognosis [ 20 ]. Zhang et al demonstrated an increased expression of PD-L1 in patients with upper urogenital tract carcinoma and that PD-L1 expression is an independent predictor of decreased cancer survival [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of programmed cell death ligand 1 in patients with CIN and its correlation with human papillomavirus infection and CIN persistence

Usta

Altun

Afşar

et al. 2020

Infect Agents Cancer

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Backround HPV causes specific cell-mediated immunity in the cervix. Mononuclear cells such as helper T cells (CD4+), cytotoxic T cells (CD8+), and dendritic cells play a critical role in the initiation of the HPV-specific immune response and destruction of virus-infected cervical epithelial cells. The programmed cell death ligand 1 (PD-L1) gene encodes an immune inhibitory receptor ligand and overexpression of PD-L1 inhibits T-cell activation and cytokine production. The aim of this study was to investigate the expression of PD-L1 in cervical tissue and its correlation with clinicopathological findings. Methods In this cross-sectional study, a total of 94 women who were referred for colposcopy due to abnormal Papanicolaou (PAP) test results and/or HPV positivity were evaluated. The presence of HR-HPV–DNA was analyzed using type- and gene-specific primers along with commercial real-time polymerase chain reaction. The cervical examination was done with a colposcope. Cervical biopsies were obtained from the areas that were evaluated as abnormal during the colposcopy. Histopathological result of cervical biopsies were defined as no intraepithelial neoplasia (CIN 0), mild CIN (CIN I), and moderate-to-high CIN (CIN II-III). All women were classified into four groups based on their HR-HPV positivity and cervical biopsy results: Group I (controls; n = 29), HR-HPV (−) CIN 0; Group II ( n = 21), HR-HPV (+) CIN 0; Group III ( n = 20), HR-HPV (+) CIN I; and Group IV ( n = 24), HR-HPV (+) CIN II-III. A semi-quantitative scoring system was used to evaluate the degree of Ki-67, p16, and PD-L1 immunoreactivity in the cervical tissue samples. Results We found that PD-L1 expression in both mononuclear cells and in cervical epithelial cells gradually increases from the HR-HPV (−), CIN 0 group to the HR-HPV (+), CIN II-III group ( p = 0.0003 and p = 0.0394, respectively) and mononuclear PD-L1 expression was correlated with HPV type, initial Pap test results, HPV persistence, and CIN persistence or recurrence ( p = 0.0180, p = 0.0109, p = 0.0042, and p = 0.0189, respectively). Moreover, mononuclear PD-L1 expression was also correlated with Ki-67 and p16 immunoreactivity ( p = 0.0432 and p = 0.0166, respectively). Epithelial PD-L1 expression was only correlated with HPV type and the presence of HPV persistence ( p = 0.0122 and p = 0.0292, respectively). Conclusion During the initial evaluation of the cervical histology results, the assessment of PD-L1 expression—especially in mononuclear cells in cervical tissue samples—may provide more information on the progr...

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“…With regard to immune checkpoints, high levels of CTLA4 and PD1/PD-L1 are often detected in CC patients, and PD1/PD-L1 are frequently expressed in dendritic cells in Cervical Intraepithelial Neoplasia (CIN) samples [24,25]. PD1/PD-L1 expression has been shown to be present in 95% of intraepithelial lesions and around 80% of squamous carcinomas [26][27][28].…”

Section: Rationale For Immunotherapy In CCmentioning

confidence: 99%

Immunotherapy and Its Development for Gynecological (Ovarian, Endometrial and Cervical) Tumors: From Immune Checkpoint Inhibitors to Chimeric Antigen Receptor (CAR)-T Cell Therapy

Schepisi

Casadei

Toma

et al. 2021

Cancers

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Gynecological tumors are malignancies with both high morbidity and mortality. To date, only a few chemotherapeutic agents have shown efficacy against these cancer types (only ovarian cancer responds to several agents, especially platinum-based combinations). Within this context, the discovery of immune checkpoint inhibitors has led to numerous clinical studies being carried out that have also demonstrated their activity in these cancer types. More recently, following the development of chimeric antigen receptor (CAR)-T cell therapy in hematological malignancies, this strategy was also tested in solid tumors, including gynecological cancers. In this article, we focus on the molecular basis of gynecological tumors that makes them potential candidates for immunotherapy. We also provide an overview of the main immunotherapy studies divided by tumor type and report on CAR technology and the studies currently underway in the area of gynecological malignancies.

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The immune checkpoints CTLA-4 and PD-L1 in carcinomas of the uterine cervix

Cited by 31 publications

References 27 publications

A novel prognostic prediction model based on seven immune-related RNAs for predicting overall survival of patients in early cervical squamous cell carcinoma

A novel prognostic prediction model based on seven immune-related RNAs for predicting overall survival of patients in early cervical squamous cell carcinoma

Overexpression of programmed cell death ligand 1 in patients with CIN and its correlation with human papillomavirus infection and CIN persistence

Immunotherapy and Its Development for Gynecological (Ovarian, Endometrial and Cervical) Tumors: From Immune Checkpoint Inhibitors to Chimeric Antigen Receptor (CAR)-T Cell Therapy

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