The Th17/Treg balance and the expression of related cytokines in Uygur cervical cancer patients

Chen, Zhifang; Ding, Jianbing; Pang, Nannan; Du, Rong; Wang, Meng; Zhu, Yuejie; Zhang, Yi; Ma, Cailing; Ding, Yan

doi:10.1186/1746-1596-8-61

Cited by 60 publications

(59 citation statements)

References 22 publications

(20 reference statements)

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“…Higher frequencies of CD4 þ and CD8 þ T cells expressed the immune checkpoint molecules PD-1 and CTLA-4, and, as expected, higher proportions of suppressive CD4þ and CD8 þ Tregs were present in LN þ (12). Also, increased levels of Tregs have been reported to be present at the site of the primary tumor (7) and in the peripheral blood of patients with cervical intraepithelial neoplasia (CIN) or cervical cancer (16). Of note, we previously reported that high Treg frequencies in the peripheral blood were associated with high-grade CINIII lesions and persistent HPV16 infection (17).…”

Section: Discussionmentioning

confidence: 58%

High and Interrelated Rates of PD-L1+CD14+ Antigen-Presenting Cells and Regulatory T Cells Mark the Microenvironment of Metastatic Lymph Nodes from Patients with Cervical Cancer

Heeren

Koster

Samuels

et al. 2015

Cancer Immunology Research

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A better understanding of the microenvironment in relation to lymph node metastasis is essential for the development of effective immunotherapeutic strategies against cervical cancer. In the present study, we investigated the microenvironment of tumor-draining lymph nodes of patients with cervical cancer by comprehensive flow cytometry-based phenotyping and enumeration of immune-cell subsets in tumor-negative (LN(-), n = 20) versus tumor-positive lymph nodes (LN(+), n = 8), and by the study of cytokine release profiles (n = 4 for both LN(-) and LN(+)). We found significantly lower CD4(+) and higher CD8(+) T-cell frequencies in LN(+) samples, accompanied by increased surface levels of activation markers (HLA-DR; ICOS; PD-1; CTLA-4) and the memory marker CD45RO. Furthermore, in LN(+), we found increased rates of a potentially regulatory antigen-presenting cell (APC) subset (CD11c(hi)CD14(+)PD-L1(+)) and of myeloid-derived suppressor cell subsets; the LN(+) APC subset correlated with significantly elevated frequencies of FoxP3(+) regulatory T cells (Treg). After in vitro stimulation with different Toll-like receptor (TLR) ligands (PGN; Poly-IC; R848), we observed higher production levels of IL6, IL10, and TNFα but lower levels of IFNγ in LN(+) samples. We conclude that, despite increased T-cell differentiation and activation, a switch to a profound immune-suppressive microenvironment in LN(+) of patients with cervical cancer will enable immune escape. Our data indicate that the CD14(+)PD-L1(+) APC/Treg axis is a particularly attractive and relevant therapeutic target to specifically tackle microenvironmental immune suppression and thus enhances the efficacy of immunotherapy in patients with metastasized cervical cancer.

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Section: Discussionmentioning

confidence: 58%

High and Interrelated Rates of PD-L1+CD14+ Antigen-Presenting Cells and Regulatory T Cells Mark the Microenvironment of Metastatic Lymph Nodes from Patients with Cervical Cancer

Heeren

Koster

Samuels

et al. 2015

Cancer Immunology Research

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“…morbidity and mortality rate of cervical cancer in Uyghur women have been found to be significantly higher than any other ethnic group (459/100,000-590/100,000 vs. 15.78/100,000) [6] .…”

mentioning

confidence: 99%

Correlation between Methylation of Human Papillomavirus-16 L1 Gene and Cervical Carcinoma in Uyghur Women

Niyazi

Sui²,

Zhu³

et al. 2016

Gynecol Obstet Invest

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Background: This study aims at determining the correlation between CpG methylation in human papillomavirus (HPV)-16 L1 and the persistent infections and development of cervical carcinoma in Uyghur women. Methods: Among the 4,364 Uyghur women, specimens were collected from 145 (3.3%) HPV-16 single infected cases, which were divided into 5 groups: transient infection (n = 32), persistent infection (n = 21, 12 months), cervical intraepithelial neoplasia (CIN) grade 1 (CIN1, n = 21), CIN2-3 (n = 33) and invasive cervical cancer (n = 38) groups. Methylation level in HPV-16 L1 was quantified by pyrosequencing, and values in the prediction and diagnosis of CIN2+ lesions were evaluated with receiver operating characteristic curves. Results: With the progression of the disease, increased methylation was detected at 13 CpG sites, and a high methylation level was associated with the risk of CIN2+. The strongest related site was 6650 (OR 9.89, 95% CI 3.57-27.44). The area under ROC curve (AUC) of methylation at each CpG site to differentiate between CIN2+ and

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“…CIN have higher levels of Tregs than normal tissues, and the presence of Tregs increases further in cancers 367 . 365,368–371 . Treg levels are correlated with a failure of lesions to regress 334 .…”

Section: Immune Interactionsmentioning

confidence: 99%

The Interaction Between Human Papillomaviruses and the Stromal Microenvironment

Woodby

Scott

Bodily

2016

Progress in Molecular Biology and Translational Science

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Human papillomaviruses (HPV) are small, double-stranded DNA viruses that replicate in stratified squamous epithelia and cause a variety of malignancies. Current efforts in HPV biology are focused on understanding the virus-host interactions that enable HPV to persist for years or decades in the tissue. The importance of interactions between tumor cells and the stromal microenvironment has become increasingly apparent in recent years, but how stromal interactions impact the normal, benign life cycle of HPVs or progression of lesions to cancer is less understood. Furthermore, how productively replicating HPV impacts cells in the stromal environment is also unclear. Here we bring together some of the relevant literature on keratinocyte-stromal interactions and their impacts on HPV biology. We discuss how HPV oncogenes in infected cells manipulate other cells in their environment, and, conversely, how neighboring cells may impact the efficiency or course of HPV infection.

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The Th17/Treg balance and the expression of related cytokines in Uygur cervical cancer patients

Cited by 60 publications

References 22 publications

High and Interrelated Rates of PD-L1+CD14+ Antigen-Presenting Cells and Regulatory T Cells Mark the Microenvironment of Metastatic Lymph Nodes from Patients with Cervical Cancer

High and Interrelated Rates of PD-L1+CD14+ Antigen-Presenting Cells and Regulatory T Cells Mark the Microenvironment of Metastatic Lymph Nodes from Patients with Cervical Cancer

Correlation between Methylation of Human Papillomavirus-16 L1 Gene and Cervical Carcinoma in Uyghur Women

The Interaction Between Human Papillomaviruses and the Stromal Microenvironment

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