Immunotherapy and Its Development for Gynecological (Ovarian, Endometrial and Cervical) Tumors: From Immune Checkpoint Inhibitors to Chimeric Antigen Receptor (CAR)-T Cell Therapy

Schepisi, Giuseppe; Casadei, Chiara; Toma, I.; Poti, Giulia; Iaia, Maria Laura; Farolfi, Alberto; Conteduca, Vincenza; Lolli, Cristian; Ravaglia, Giorgia; Brighi, Nicole; Altavilla, Amelia; Martinelli, Giovanni; Giorgi, Ugo De

doi:10.3390/cancers13040840

Cited by 23 publications

(21 citation statements)

References 111 publications

(123 reference statements)

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“…At present, since the role of T cells in cancer immunity has been widely understood, more and more studies have been conducted on chimeric antigen receptor (CAR)-T cell therapy for cervical cancer. Unfortunately, unlike hematologic malignancies, cervical cancer is a solid tumor that may result in CAR-T cell depletion due to protection by the immune-silencing microenvironment [ 45 ]. RGS1 mediates T cell retention, leading to T cell depletion, which may be a target for improved CAR-T therapy in cervical cancer.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Immunotherapy has been applied in clinical pathology at a robust rate due to promising effects in numerous solid tumors, including gynecologic tumors. [23][24][25] However, the role of PD-L1 expression has not been clear in ESCs, largely due to limited available survival-based evidence. In this study, we analyzed PD-L1 expression in ESC tumors and correlated its expression with clinicopathologic parameters and survival outcomes to enhance our understanding of the role of the PD-1/PD-L1 pathway as a potential therapeutic target for this kind of tumor.…”

Section: Discussionmentioning

confidence: 99%

PD-L1 Expression in Endometrial Serous Carcinoma and Its Prognostic Significance

Zhang¹,

Q²,

Zhu³

et al. 2021

CMAR

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Purpose Programmed death-ligand 1 (PD-L1) has been widely used as a prognostic biomarker and an immunotherapeutic target in numerous cancers, but information on the clinical significance of its expression in endometrial serous carcinoma (ESC) is largely lacking. Here, we evaluate the predictive value of PD-L1 expression in ESC. Materials and Methods A total of 79 cases of ESC accessioned between January 2003 and September 2015 were selected for further analysis. PD-L1 expression was evaluated in whole tissue sections of these cases by using the tumor proportion score (TPS, cut-off 1%) and combined positive score (CPS, cut-off 1) scoring methods. Results Overall, there was a heterogeneous expression of PD-L1, focal or patchy, in ESCs. PD-L1 positivity was observed in 43.0% of ESCs by TPS and 73.4% of ESCs by CPS. Kaplan–Meier survival analysis showed that patients with PD-L1-positive tumors suffered significantly worse OS and PFS, when compared with PD-L1 negative tumors (log-rank p = 0.037 and p = 0.003, respectively). In contrast, PD-L1 positivity by CPS within the ESC cases showed no statistical significance for OS and PFS (log-rank p = 0.720 and p = 0.928, respectively). Multivariate Cox analysis showed that PD-L1 positivity by TPS was significantly associated with PFS (HR = 1.921, p = 0.039) but not OS (HR = 1.229, p = 0.631). Conclusion PD-L1 expression is frequently found in ESC, suggesting a potential role of the PD-1/PD-L1 pathway as a potential therapeutic target for these tumors. PD-L1 expression by TPS also serves as a negative prognostic marker in ESC and implies an unfavorable outcome.

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“…However, regarding gynaecological tumors, the role of immunotherapy has so far been limited [ 93 , 94 , 95 , 96 ]. The efficacy of immunotherapy has been tested in ovarian cancer; however, the results were not as expected: the main phase III immunotherapy trials conducted in ovarian cancer yielded negative results [ 97 , 98 , 99 ].…”

Section: Pd-1/pd-l1mentioning

confidence: 99%

Biomarkers of Central Nervous System Involvement from Epithelial Ovarian Cancer

Scotto

Borella

Turinetto

et al. 2021

Cells

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Epithelial ovarian cancer (EOC) is the leading cause of death among women affected by gynaecological malignancies. Most patients show advanced disease at diagnosis (FIGO stage III-IV) and, despite the introduction of new therapeutic options, most women experience relapses. In most cases, recurrence is abdominal-pelvic; however, EOC can occasionally metastasize to distant organs, including the central nervous system. The incidence of brain metastases (BMs) from EOC is low, but it has grown over time; currently, there are no follow-up strategies available. In the last decade, a few biomarkers able to predict the risk of developing BMs from OC or as potential therapeutic targets have been investigated by several authors; to date, none have entered clinical practice. The purpose of this review is to offer a summary on the role of the most relevant predictors of central nervous system (CNS) involvement (hormone receptors; BRCA; MRD1; PD-1/PD-L1) and to highlight possible therapeutic strategies for the management of metastatic brain disease in EOC

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Immunotherapy and Its Development for Gynecological (Ovarian, Endometrial and Cervical) Tumors: From Immune Checkpoint Inhibitors to Chimeric Antigen Receptor (CAR)-T Cell Therapy

Cited by 23 publications

References 111 publications

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

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

PD-L1 Expression in Endometrial Serous Carcinoma and Its Prognostic Significance

Biomarkers of Central Nervous System Involvement from Epithelial Ovarian Cancer

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