The Role of Immunotherapy in the Treatment of Advanced Cervical Cancer: Current Status and Future Perspectives

Walsh, Robert J.; Tan, David S.P.

doi:10.3390/jcm10194523

Cited by 16 publications

(13 citation statements)

References 87 publications

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“…However, many advanced patients, especially those with low‐PD‐1/PD‐L1 expression, are not sensitive to immunocheckpoint inhibitor therapy. 43 Our study provides the possibility for the combination of Nr‐CWS with PD‐1/PD‐L1 antibody. A large number of studies have shown that radiation therapy can affect the tumor microenvironment, resulting in increased PD‐L1 side effects in tumor tissues.…”

Section: Discussionmentioning

confidence: 82%

Nocardia rubra cell‐wall skeleton influences the development of cervical carcinoma by promoting the antitumor effect of macrophages and dendritic cells

et al. 2022

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Background As an immune enhancer, Nocardia rubra cell‐wall skeleton (Nr‐CWS) has been used to treat persistent human papillomavirus infection and cervical precancerous lesions. However, it is still unclear whether it can be used to treat cervical carcinoma. Methods In our study, the aim was to determine whether Nr‐CWS affects the apoptosis of cervical carcinoma cells by enhancing the antitumor effect of dendritic cells and macrophages in vivo and in vitro. Results The experimental results showed that Nr‐CWS can promote the activity of dendritic cells and macrophages and reduce their apoptosis. It also increased the cytokines IL‐6, IL‐12, TNF‐ɑ, and IL‐1β secreted by dendritic cells and macrophages and reduced their PD‐L1 expression. In vitro, Nr‐CWS inhibited the proliferation, colony forming ability of HeLa and SiHa cervical carcinoma cell lines cultured with macrophages, and more cells were blocked in G2/M phase. Nr‐CWS promoted TNF‐ɑ/TNFR1/caspase‐8‐mediated apoptosis by increasing macrophages secretion of TNF‐ɑ and inhibited cell migration and invasion regulated by the WNT/β‐catenin‐EMT pathway. Nr‐CWS also reduced the expression of the cervical carcinoma genes E6 and E7 thereby increasing expression of p53 gene and decreasing expression of PD‐L1 gene. In vivo, Nr‐CWS inhibited tumor growth and decreased the expression of E6, E7, PD‐L1, P16, Ki67, and PCNA in tumors. Conclusions Therefore, our results suggest that Nr‐CWS can promote apoptosis of cervical carcinoma cells by enhancing the antitumor effect of dendritic cells and macrophages.

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Section: Discussionmentioning

confidence: 82%

Nocardia rubra cell‐wall skeleton influences the development of cervical carcinoma by promoting the antitumor effect of macrophages and dendritic cells

et al. 2022

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“…As screening and largely also treatment appear to have reached their limits, the fight against cervical, vaginal and other HPV-related cancer is now relying on HPV vaccination which may have global preventive perspectives which screening was not able to fulfill [ 39 – 41 , 50 , 51 ]. With regard to treatment of metastatic cervical cancer, immunotherapy appears to provide a much-needed increase in efficacy [ 52 , 53 ]. The presence of foreign viral proteins resulting from HPV infection facilitates use of immunotherapy for treatment of these tumor types.…”

Section: Discussionmentioning

confidence: 99%

Cervical, vaginal and vulvar cancer incidence and survival trends in Denmark, Finland, Norway and Sweden with implications to treatment

et al. 2022

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Background Incidence of cervical cancer has been reduced by organized screening while for vaginal and vulvar cancers no systematic screening has been implemented. All these cancers are associated with human papilloma virus (HPV) infection. We wanted to analyze incidence trends and relative survival in these cancers with specific questions about the possible covariation of incidence, survival changes coinciding with incidence changes and the role of treatment in survival. We used nationwide cancer registry data for Denmark (DK), Finland (FI), Norway (NO) and Sweden (SE) to address these questions. Methods We use the NORDCAN database for the analyses: incidence data were available from 1943 in DK, 1953 in FI and NO and 1960 in SE, through 2016. Survival data were available from 1967 through 2016. World standard population was used in age standardization. Results In each country the incidence of cervical cancer declined subsequent to rolling out of screening activities. The attained plateau incidence was lowest at 4/100,000 in FI and highest at 10/100,000 in DK and NO. The incidence of vaginal and vulvar cancer remained relatively constant at about 2/100,000. Relative 1-year survival in cervical cancer improved in all countries from low 80%s to high 80%s in the 50-year period, and 5-year survival improved also but at 20% units lower level. Survival gains were found only in patients diagnosed before age 60 years. Survival in vaginal and vulvar cancer followed the same patterns but at a few % units lower level. Conclusion Cervical cancer screening appeared to have reached its limits in the Nordic countries by year 2000. Novel treatments, such as immunotherapy, would be needed to improve survival until HPV vaccination will reach population coverage and boost the global fight against these cancers.

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“…The use of ICIs has greatly changed the therapeutic pattern for many solid organ malignancies. An ever-increasing number of targets have been identified, and relevant studies have made people have provided better insight into the underlying mechanism and efficacy of ICIs in cervical cancer treatment [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

RGS1 and related genes as potential targets for immunotherapy in cervical cancer: computational biology and experimental validation

et al. 2022

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Background Effective treatment is needed for advanced, inoperable, or chemotherapy-resistant cervical cancer patients. Immunotherapy has become a new treatment modality for cervical cancer patients, and there is an urgent need to identify additional targets for cervical cancer immunotherapy. Methods In this study the core gene, RGS1, which affects immune status and the FIGO stage of cervical cancer patients was identified by WGCNA analysis and differential analysis using TCGA database. 10 related genes interacting with RGS1 were identified using PPI network, and the functional and immune correlations were analyzed. Based on the expression of RGS1 and related genes, the consensus clustering method was used to divide CESC patients into two groups (group 1, high expression of RGS1; group 2, low expression of RGS1). Then, the functional enrichment analysis was used to search for the functional differences in differentially expressed genes (DEGs) between group 1 and group 2. Immune infiltration analysis was performed using ESTIMATE, CIBERSORT, and ssGSEA, and the differences in expression of immune checkpoint inhibitors (ICIs) targets were assessed between the two groups. We investigated the effect of RGS1 on the clinical relevance of CESC patients, and experimentally verified the differences in RGS1 expression between cervical cancer patient tissues and normal cervical tissues, the role of RGS1 in cell function, and the effect on tumor growth in tumor-bearing mice. Results We found that RGS1 was associated with CD4, GNAI3, RGS2, GNAO1, GNAI2, RGS20, GNAZ, GNAI1, HLA-DRA and HLA-DRB1, especially CD4 and RGS2. Functional enrichment of DEGs was associated with T cell activation. Compared with group 2, group 1 had stronger immune infiltration and higher ICI target expression. RGS1 had higher expression in cervical cancer tissues than normal tissues, especially in HPV-E6 positive cancer tissues. In cervical cancer cell lines, knockdown of RGS1 can inhibited cell proliferation, migration, invasion, and tumor growth in nude mice and promoted apoptosis. Conclusions RGS1, as an oncogenic gene of cervical cancer, affects the immune microenvironment of patients with cervical cancer and may be a target of immunotherapy.

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The Role of Immunotherapy in the Treatment of Advanced Cervical Cancer: Current Status and Future Perspectives

Cited by 16 publications

References 87 publications

Nocardia rubra cell‐wall skeleton influences the development of cervical carcinoma by promoting the antitumor effect of macrophages and dendritic cells

Nocardia rubra cell‐wall skeleton influences the development of cervical carcinoma by promoting the antitumor effect of macrophages and dendritic cells

Cervical, vaginal and vulvar cancer incidence and survival trends in Denmark, Finland, Norway and Sweden with implications to treatment

RGS1 and related genes as potential targets for immunotherapy in cervical cancer: computational biology and experimental validation

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