Immunotherapy for Uterine Cervical Cancer Using Checkpoint Inhibitors: Future Directions

Kagabu, Masahiro; Nagasawa, Takayuki; Sato, Chie; Fukagawa, Yasuko; Kawamura, Hanae; Tomabechi, Hidetoshi; Takemoto, Shuji; Shoji, Tadahiro; Baba, Tsukasa

doi:10.3390/ijms21072335

Cited by 71 publications

(51 citation statements)

References 29 publications

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“…Besides, accumulating evidence has indicated that tumor-specific mutations could generate neoantigens, thus activating the immunological recognition and killing the tumor cells, indicating that modification of some specific genes could influence the status of TME ( Turajlic et al, 2017 ; Smith et al, 2019 ). In addition, immunotherapy targeting ICPs had achieved tremendous success in multiple human cancers worldwide ( Sun et al, 2020 ), including CC ( Kagabu et al, 2020 ). However, the responses to immunotherapy using ICIs were relatively low in CC patients, and we could not ignore its immune-related adverse reactions ( Frenel et al, 2017 ; Rischin et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated Bioinformatical Analysis Identifies GIMAP4 as an Immune-Related Prognostic Biomarker Associated With Remodeling in Cervical Cancer Tumor Microenvironment

Shen

2021

Front. Cell Dev. Biol.

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Tumor microenvironment (TME) is emerging as an essential part of cervical cancer (CC) tumorigenesis and development, becoming a hotspot of research these years. However, comprehending the specific composition of TME is still facing enormous challenges, especially the immune and stromal components. In this study, we downloaded the RNA-seq profiles and somatic mutation data of 309 CC cases from The Cancer Genome Atlas (TCGA) database, which were analyzed by integrative bioinformatical methods. Initially, ESTIMATE computational method was employed to calculate the amount of immune and stromal components. Then, based on the high- and low-immunity cohorts, we recognized the differentially expressed genes (DEGs) as well as the differentially mutated genes (DMGs). Additionally, we conducted an intersection analysis of DEGs and DMGs, ultimately determining an immune-related prognostic signature, GTPase, IMAP Family Member 4 (GIMAP4). Moreover, sequential analyses demonstrated that GIMAP4 was a protective factor in CC, positively correlated with the overall survival (OS) and negatively with distant metastasis. Besides, we utilized the Gene Set Enrichment Analysis (GSEA) to explore the enrichment-pathways in high and low-expression cohorts of GIMAP4. The results indicated that the genes of the high-expression cohort had a high enrichment in immune-related biological processes and metabolic activities in the low one. Furthermore, CIBERSORT analysis was applied to evaluate the proportion of tumor-infiltrating immune cells (TICs), illustrating that several activated TICs were strongly associated with GIMAP4 expression, which suggested that GIMAP4 had the potential to be an indicator for the immune state in TME of CC. Hence, GIMAP4 contributed to predicting the CC patients’ clinical outcomes, such as survival rate, distant metastasis and immunotherapy response. Moreover, GIMAP4 could serve as a promising biomarker for TME remodeling, suggesting the possible underlying mechanisms of tumorigenesis and CC progression, which may provide different therapeutic perceptions of CC, and therefore improve treatment.

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Section: Discussionmentioning

confidence: 99%

Integrated Bioinformatical Analysis Identifies GIMAP4 as an Immune-Related Prognostic Biomarker Associated With Remodeling in Cervical Cancer Tumor Microenvironment

Shen

2021

Front. Cell Dev. Biol.

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“…Conventional treatment options for metastatic/recurrent cervical cancer additionally includes radiotherapy and chemotherapy, and this treatment is most often not sufficiently effective for disease management at this late stage. Global reports indicate that in 2018, there were about 569,000 cases of cervical cancer worldwide, with 311,000 deaths [134]; Cancer Fact Sheets: Cervical Cancer. http://gco.iarc.fr/today/data/pdf/factsheets/cancers/cancer-fact-sheets-16.…”

Section: Cervical and Other Female Gynecologic Cancersmentioning

confidence: 99%

“…The distribution of PD-L1 is on the surface of cervical cancer cells, TILs, and APCs, with PD-1 on T cells in the stroma of cervical cancer. The PD-1/PD-L1 axis has been targeted in several clinical trials [25,134], some of which are noteworthy in this report.…”

Section: Cervical and Other Female Gynecologic Cancersmentioning

confidence: 99%

Immune Checkpoint Blockade in Gynecologic Cancers: State of Affairs

Drakes

Czerlanis

Stiff

2020

Cancers

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This review provides an update on the current use of immune checkpoint inhibitors (ICI) in female gynecologic cancers, and it addresses the potential of these agents to provide therapy options for disease management and long-term remission in advanced disease patients, where surgery, chemotherapy, and/or radiation fail to meet this goal. The topic of immune checkpoint inhibitors (ICI) blocking cytotoxic T lymphocyte associated protein-4 (CTLA-4) and the programmed death-1 (PD-1) axis has come to the forefront of translational medicine over the last decade for several malignancies. The text will focus primarily on a discussion of ovarian cancer, which is the most frequent cause of death of gynecologic cancers; endometrial cancer, which is the most often diagnosed gynecologic cancer; and cervical cancer, which is the third most common female gynecologic malignancy, all of which unfavorably alter the lives of many women. We will address the critical factors that regulate the outcome of these cancer types to ICI therapy, the ongoing clinical trials in this area, as well as the adverse immune responses that impact the outcome of patients given ICI regimens.

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“…In the past five years, the treatment of recurrent and advanced cervical cancer has improved significantly. However, the average overall survival period of advanced cervical cancer is 16.8 months, and the 5-year overall survival rate of all stages is only 68% [3], which has a great impact and harm on patients' living standard and prognosis.…”

Section: Introductionmentioning

confidence: 99%

The Potential of circRNA as a Novel Diagnostic Biomarker in Cervical Cancer

Chen

Yang

et al. 2021

Journal of Oncology

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Cervical cancer is the fourth most common cancer among females worldwide. In spite of advances in detection and treatment, it is still one of the most dangerous gynecological malignancies in the world, especially in developing countries, and seriously threatens human health. Circular RNA (circRNA) is a special new type of endogenous noncoding RNA discovered recently. They form a covalently closed continuous loop and are specifically expressed in the eukaryotic transcriptome. With further understanding of circular RNA, a large number of studies have determined the key regulatory role of circRNA in a variety of diseases, especially cancer (including cervical cancer, liver cancer, and lung cancer). In addition, it has also been found that the abnormal expression of circRNA is related to its pathological characteristics in cervical cancer tissue, which can be used as a potential indicator for early screening and diagnosis of cervical cancer, targeted therapy, and prognosis prediction. This article summarizes the recent research achievements of circRNAs in cervical cancer. We briefly described the abnormal expression of circRNA in cervical cancer and discussed the involvement of circRNA in the occurrence process of cervical cancer by regulating cell proliferation, migration, invasion, and apoptosis. We believe that circRNA has potential value as a biomarker in the diagnosis and prognosis of cervical cancer.

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Immunotherapy for Uterine Cervical Cancer Using Checkpoint Inhibitors: Future Directions

Cited by 71 publications

References 29 publications

Integrated Bioinformatical Analysis Identifies GIMAP4 as an Immune-Related Prognostic Biomarker Associated With Remodeling in Cervical Cancer Tumor Microenvironment

Integrated Bioinformatical Analysis Identifies GIMAP4 as an Immune-Related Prognostic Biomarker Associated With Remodeling in Cervical Cancer Tumor Microenvironment

Immune Checkpoint Blockade in Gynecologic Cancers: State of Affairs

The Potential of circRNA as a Novel Diagnostic Biomarker in Cervical Cancer

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