scholarly journals Elevated Expression of Programmed Death-1 and Programmed Death Ligand-1 Negatively Regulates Immune Response against Cervical Cancer Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Zhifang Chen ◽  
Nannan Pang ◽  
Rong Du ◽  
Yuejie Zhu ◽  
Lingling Fan ◽  
...  

The present study is to measure the expression of programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1), as well as its clinical significance in cervical cancer patients. Our results showed that different T cell subsets in patients with cervical cancer had high expression of PD-1, and DCs had high expression of PD-L1. High expression of PD-1 on Treg cells in cervical cancer patients facilitated the production of TGF-βand IL-10 but inhibited the production of IFN-γ. Cervical cancer elevated the expression of PD-1 and PD-L1 in mRNA level. PD-1 expression in peripheral blood of cervical cancer patients was related with tumor differentiation, lymph node metastasis, and invasiveness. PD-1/PD-L1 pathway inhibited lymphocyte proliferation but enhanced the secretion of IL-10 and TGF-βin vitro. In summary, our findings demonstrate that elevated levels of PD-1/PD-L1, TGF-β, and IL-10 in peripheral blood of cervical cancer patients may negatively regulate immune response against cervical cancer cells and contribute to the progression of cervical cancer. Therefore, PD-1/PD-L1 pathway may become an immunotherapy target in the future.

1997 ◽  
Vol 15 (3) ◽  
pp. 1008-1012 ◽  
Author(s):  
C C Pao ◽  
J J Hor ◽  
F P Yang ◽  
C Y Lin ◽  
C J Tseng

PURPOSE To determine the presence of cervical cancer cells in circulating peripheral blood of stage IVb cervical cancer patients with metastasis to distant organs. PATIENTS AND METHODS Cervical cancer tissue from 15 stage IVb cervical cancer patients with metastasis were analyzed for the presence of human papillomavirus (HPV) type 16 DNA by nested polymerase chain reaction (PCR). The presence of transcriptional products of the HPV type 16 E6-transforming gene in the peripheral blood of the same 15 cancer patients was analyzed by reverse transcription and PCR. Cervical tissues and peripheral-blood specimens from 12 normal healthy individuals served as controls. RESULTS Thirteen of 15 (86.7%) cervical cancer tissues from same number of patients were found to contain HPV type 16 DNA. Peripheral-blood specimens from 12 of 13 (92.3%) cervical HPV DNA-positive patients were found to contain HPV-specific mRNA detectable by reverse transcription (RT) and PCR. Cervical tissues from all 12 normal controls were HPV-free. None of the peripheral-blood specimens from two cervical HPV-negative cancer patients and 12 normal controls contained detectable amounts of mRNA of HPV type 16 E6-transforming gene. CONCLUSION The most likely source of the HPV-specific mRNA detected in the peripheral blood of cervical cancer patients with metastasis is the cervical cancer cells derived from or shed from the cervix. The presence of HPV E6 mRNAs in peripheral blood may be a sensitive indicator of circulating cervical cancer cells. If PCR positivity is proven to be able to predict disease progression reliably, these findings may have clinical applications in the treatment of cervical and many other cancers.


2022 ◽  
Author(s):  
Hanxiang Chen ◽  
Yongqing Li ◽  
Shaoming Zhang ◽  
Yunshan Wang ◽  
Lili Wang ◽  
...  

Abstract Background As one of the most common cancer among women worldwide, the prognosis of patients with advanced cervical cancer remains unsatisfactory. A study indicated that transmembrane protein 33 (TMEM33) was implicated in tumor recurrence, while its role in cervical cancer has not been elucidated. Methods TMEM33 expression in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) was primarily screened in The Cancer Genome Altas (TCGA), and further validated in Gene Expression Omnibus (GEO) database. The Kaplan–Meier plotter analysis and Cox regression were constructed to evaluate the prognostic value of TMEM33 in CESC. Functional enrichment analysis was performed with GO, KEGG and GSEA tools. Protein-protein interaction analysis and correlated gene networks were conducted using STING and GEPIA2 websites, respectively. The expression of TMEM33 in cervical cancer cells were examined by immunoblotting and RT-qPCR. Finally, CCK-8 assay and colony formation assay were performed to investigate the role of TMEM33 in cervical cancer cell proliferation. Results TMEM33 expression was significantly elevated in CESC compared with normal tissues. High expression of TMEM33 was associated with poor prognostic clinical characteristics in CESC patients. KM-plotter analysis revealed that patients with increased TMEM33 had shorter overall survival (OS), progress free interval (PFI), and disease specific survival (DSS). Moreover, Multivariate Cox analysis further confirmed that high TMEM33 expression was an independent risk factor for OS in patients with CESC. TMEM33 was associated with immune cell infiltration, and its expression was correlated with tumorigenesis-related genes RNF4, OCIAD1, TMED5, DHX15, MED28 and LETM1. More importantly, knockdown of TMEM33 in cervical cancer cells decreased the expression of those genes and inhibited cell proliferation. Conclusions Increased TMEM33 in cervical cancer can serve as an independent prognostic marker and might play a role in tumorigenesis by promoting cell proliferation.


2013 ◽  
Vol 4 ◽  
Author(s):  
L�pez Pulido Edgar ◽  
Mu�oz Valle Jos� ◽  
Pereira Su�rez Ana ◽  
Del Toro Arreola Susana ◽  
Ascencio Cedillo Rafael ◽  
...  

2016 ◽  
Vol 213 (13) ◽  
pp. 2835-2840 ◽  
Author(s):  
Antoni Ribas ◽  
Siwen Hu-Lieskovan

Expression of the programmed death-1 (PD-1) ligand 1 (PD-L1) is used to select patients and analyze responses to anti–PD-1/L1 antibodies. The expression of PD-L1 is regulated in different ways, which leads to a different significance of its presence or absence. PD-L1 positivity may be a result of genetic events leading to constitutive PD-L1 expression on cancer cells or inducible PD-L1 expression on cancer cells and noncancer cells in response to a T cell infiltrate. A tumor may be PD-L1 negative because it has no T cell infiltrate, which may be reversed with an immune response. Finally, a tumor that is unable to express PD-L1 because of a genetic event will always be negative for PD-L1 on cancer cells.


2021 ◽  
Vol 13 (8) ◽  
pp. 1506-1511
Author(s):  
Minjuan Xu ◽  
Jun Huang ◽  
Liefeng Wang

Cervical cancer is often treated with surgery, radiotherapy and chemotherapy, but it does not have the advantages of precise treatment and prognosis is not ideal. Molecular targeted therapy can make up for the above shortcomings. This study mainly analyzed the influence of miR-126 on cervical cancer cells and possible molecular mechanisms, so as to provide a reference for better clinical improvement of prognosis for cervical cancer. C33a cells were assigned into control group, empty carrier group (C33a cells were co-cultured with liposome nanoparticle carrier), inhibitor group (C33a cells were treated with PD-1/PD-L1 signaling pathway inhibitor), miR-126 group (miR-126 with liposomal nanoparticles as carrier was added to C33a cells), followed by expression analysis of miR-126 and AK2, cell proliferation, PD-1/PD-L1 signaling and phosphorylation levels, as well as tumor mass and volume in nude mice. At 24 h, no difference of cell proliferation was found (P > 0.05) but cell proliferation showed significant differences after cell growth of 48 h, with lower proliferation in inhibitor group and miR-126 group (P < 0.05). The levels of PD-1, PD-L1, AK2, and p-PD-1 in inhibitor group and miR-126 group were significantly lower than for the other two groups (P > 0.05). There was a target relationship between miR-126 and AK2. The transplanted tumor in the miR-126 group was significantly decreased, with lower tumor mass and volume than control group (P < 0.05). The carrier-based miR-126 and PD-1/PD-L1 signaling inhibitors can inhibit cervical cancer cell proliferation.


2021 ◽  
Vol 11 ◽  
Author(s):  
Sheng-Kai Huang ◽  
Ruo-Xuan Ni ◽  
Wen-Jie Wang ◽  
Di Wang ◽  
Mei Zhao ◽  
...  

ObjectiveTo study the expression of LINC00673 in cervical cancer and cervical intraepithelial neoplasia (CIN) and to explore the role of LINC00673 in the development of cervical cancer.MethodsThe expression of LINC00673 in serum from cervical cancer patients, CIN patients, and healthy participants was detected by RT-qPCR. The function of LINC00673 in cervical cancer cells was analyzed using in vitro and in vivo experiments.ResultsOur results revealed that serum LINC00673 levels were highest in cervical cancer patients, followed by patients with CIN and healthy controls. In vitro experiments demonstrated that overexpression of LINC00673 enhanced the proliferation and cell cycle progression of HeLa and SiHa cells. In vivo experiments showed that the tumor weight and volume of nude mice subcutaneously injected with LINC00673-overexpressing HeLa cells were larger than those of nude mice injected with control cells (P &lt; 0.05). Western blotting showed that cell cycle-related proteins cyclin A2 and cyclin E and interstitial-associated proteins Snail and N-cadherin were upregulated and p53 signaling pathway-related proteins were downregulated in LINC00673-overexpressing HeLa and SiHa cells.ConclusionLINC00673 plays an important role in the development of cervical cancer and may serve as a new therapeutic target for cervical cancer.


2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Yanxia Sui ◽  
Ya Yang ◽  
Ji Wang ◽  
Yi Li ◽  
Hongbing Ma ◽  
...  

Cervical cancer is the second most common cause of cancer death in women worldwide. Lysophosphatidic acid (LPA) level has been found significantly increased in the serum of patients with ovarian, cervical, and colon cancers. LPA level in cervical cancer patients is significantly higher than in healthy controls. LPA receptors were found highly expressed in cervical cancer cells, suggesting LPA may play a role in the development of cervical cancer. The aim of this study is to investigate the effect of LPA on the apoptosis induced by cisplatin (DDP) in cervical cancer cell line and the underlying changes in signaling pathways. Our study found that cisplatin induced apoptosis of Hela cell through inhibiting expression of Bcl-2, upregulating the expression of Bax, Fas-L, and the enzyme activity of caspase-3 (p<0.05); LPA significantly provided protection against the apoptosis induced by cisplatin by inhibiting the above alterations in apoptotic factor caused by cisplatin (p<0.05). Moreover, PI3K/AKT pathway was found to be important for the LPA antiapoptosis effect, and administration of PI3K/AKT partially reversed the LPA-mediated protection against cisplatin-induced apoptosis (p<0.05). These findings have shed new lights on the LPA bioactivity in cervical cancer cells and pointed to a possible sensitization scheme through combined administration of PI3K inhibitor and cisplatin for better treatment of cervical cancer patients, especially those with elevated LPA levels.


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