Immunotherapy in Cervical Cancer

Mauricio, Dennis; Zeybek, Burak; Tymon‐Rosario, Joan; Harold, Justin; Santin, Alessandro D.

doi:10.1007/s11912-021-01052-8

Cited by 56 publications

(46 citation statements)

References 49 publications

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“…The only ICI currently approved by the Food and Drug Administration (FDA) is Pembrolizumab: on 12 June 2018 approval was granted for patients with recurrent or metastatic PD-L1 positive cervical cancer with disease progression during or after chemotherapy. Pembrolizumab is a highly selective, fully humanized monoclonal antibody that blocks the PD-1 receptor expressed on T cells and inhibits the PDL1 pathway [ 35 ]. The study that led to the approval was the phase II basket trial Keynote-158 [ 36 ].…”

Section: Ici: Clinical Developmentmentioning

confidence: 99%

Immunotherapy for Cervical Cancer: Are We Ready for Prime Time?

Turinetto

Valsecchi

Tuninetti

et al. 2022

IJMS

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The prognosis of invasive cervical cancer (CC) remains poor, with a treatment approach that has remained the same for several decades. Lately, a better understanding of the interactions between the disease and the host immune system has allowed researchers to focus on the employment of immune therapy in various clinical settings. The most advanced strategy is immune checkpoint inhibitors (ICIs) with numerous phase II and III trials recently concluded with very encouraging results, assessing single agent therapy, combinations with chemotherapy and radiotherapy. Apart from ICIs, several other compounds have gained the spotlight. Tumor Infiltrating Lymphocytes (TILs) due to their highly selective tumoricidal effect and manageable adverse effect profile have received the FDA’s Breakthrough Therapy designation in 2019. The antibody drug conjugate (ADC) Tisotumab-Vedotin has shown activity in metastatic CC relapsed after at least one line of chemotherapy, with a phase III trial currently actively enrolling patients. Moreover, the deeper understanding of the ever-changing immune landscape of CC carcinogenesis has resulted in the development of active therapeutic vaccines. This review highlights the different immunotherapeutic strategies being explored reflects on what role immunotherapy might have in therapeutic algorithms of CC and addresses the role of predictive biomarkers.

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Section: Ici: Clinical Developmentmentioning

confidence: 99%

Immunotherapy for Cervical Cancer: Are We Ready for Prime Time?

Turinetto

Valsecchi

Tuninetti

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…Traditional cancer treatments, such as chemotherapy, radiotherapy, and/or surgical resection, remain the standard therapeutic approach. However, significant side effects and a narrow therapeutic window are limitations of systemic chemotherapy against advanced cervical cancer [2][3][4]. In addition, there are few treatment options for recurrent or metastatic cases.…”

Section: Introductionmentioning

confidence: 99%

“…Immune checkpoint blockade (ICB) therapy targeting the PD-L1 (e.g., atezolizumab, avelumab, and durvalumab)/PD-1 (e.g., nivolumab, pembrolizumab, Molecules 2021, 26, 5648 2 of 22 spartalizumab, and cemiplimab) axis reactivates T-cell immunity in tumor microenvironment [12]. In recent decades, the introduction of ICB therapy has fundamentally transformed the treatment landscape in various types of advanced cancers, including cervical cancer, and provided long-term survival benefits [3,[12][13][14][15][16]. On the other hands, less than 40% of patients derive clinical benefits because many cancer patients are primary and/or adaptive resistance to immune checkpoint inhibitors [17][18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Ezrin Modulates the Cell Surface Expression of Programmed Cell Death Ligand-1 in Human Cervical Adenocarcinoma Cells

et al. 2021

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Cancer cells employ programmed cell death ligand-1 (PD-L1), an immune checkpoint protein that binds to programmed cell death-1 (PD-1) and is highly expressed in various cancers, including cervical carcinoma, to abolish T-cell-mediated immunosurveillance. Despite a key role of PD-L1 in various cancer cell types, the regulatory mechanism for PD-L1 expression is largely unknown. Understanding this mechanism could provide a novel strategy for cervical cancer therapy. Here, we investigated the influence of ezrin/radixin/moesin (ERM) family scaffold proteins, crosslinking the actin cytoskeleton and certain plasma membrane proteins, on the expression of PD-L1 in HeLa cells. Our results showed that all proteins were expressed at mRNA and protein levels and that all ERM proteins were highly colocalized with PD-L1 in the plasma membrane. Interestingly, immunoprecipitation assay results demonstrated that PD-L1 interacted with ERM as well as actin cytoskeleton proteins. Furthermore, gene silencing of ezrin, but not radixin and moesin, remarkably decreased the protein expression of PD-L1 without affecting its mRNA expression. In conclusion, ezrin may function as a scaffold protein for PD-L1; regulate PD-L1 protein expression, possibly via post-translational modification in HeLa cells; and serve as a potential therapeutic target for cervical cancer, improving the current immune checkpoint blockade therapy.

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“…Cervical cancer (CC), as one of the most frequently diagnosed female malignancies, is the fourth leading cause of cancer mortality in females (1). Although current treatment strategies including surgery, chemoradiotherapy, and immunotherapy have tremendously ameliorated the prognosis, the clinical outcome of advanced cervical cancer patients is still not optimistic (2). Owing to its great threat to women's health and life, exploration of useful prognostic biomarkers and therapeutic targets for cervical cancer seems to be essential.…”

Section: Introductionmentioning

confidence: 99%

Development of a Novel Immune Infiltration-Based Gene Signature to Predict Prognosis and Immunotherapy Response of Patients With Cervical Cancer

Zhang

et al. 2021

Front. Immunol.

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Predictive models could indicate the clinical outcome of patients with carcinoma. Cervical cancer is one of the most frequently diagnosed female malignancies. Herein, we proposed an immune infiltration-related gene signature that predicts prognosis of patients with cervical cancer and depicts the immune landscape as well. We utilized the transcriptome data of The Cancer Genome Atlas (TCGA) and estimated the infiltration level of 28 immune cell types. We screened out four immune cell types conducive to patient survival and recognized their shared differentially expressed genes (DEGs). Four core genes (CHIT1, GTSF1L, PLA2G2D, and GNG8) that composed the ultimate signature were identified via univariate and multivariate Cox regression. The optimal model we built up could distinguish patients with cervical cancer into high-score and low-score subgroups. These two subgroups showed disparity in aspects of patient survival, immune infiltration landscape, and response to immune checkpoint inhibitors. Additionally, we found that GTSF1L was decreased gradually along with the severity of cervical lesions, and its potential role in immune contexture and clinical practice were also demonstrated. Our results suggested that the Immunoscore based on four immune-related genes could serve as a supplementary criterion to effectively foresee the survival outcome, tumor infiltration status, and immunotherapy efficacy of cervical cancer patients.

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Immunotherapy in Cervical Cancer

Cited by 56 publications

References 49 publications

Immunotherapy for Cervical Cancer: Are We Ready for Prime Time?

Immunotherapy for Cervical Cancer: Are We Ready for Prime Time?

Ezrin Modulates the Cell Surface Expression of Programmed Cell Death Ligand-1 in Human Cervical Adenocarcinoma Cells

Development of a Novel Immune Infiltration-Based Gene Signature to Predict Prognosis and Immunotherapy Response of Patients With Cervical Cancer

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