scholarly journals The Tumor Microenvironment of Epithelial Ovarian Cancer and Its Influence on Response to Immunotherapy

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 242 ◽  
Author(s):  
Galaxia Rodriguez ◽  
Kristianne Galpin ◽  
Curtis McCloskey ◽  
Barbara Vanderhyden
Keyword(s):  
Ovarian Cancer ◽  
Tumor Microenvironment ◽  
Epithelial Ovarian Cancer ◽  
B Lymphocytes ◽  
Immune Cells ◽  
Ovarian Cancer Cell ◽  
Cell Types ◽  
Therapeutic Approaches ◽  
Mutational Burden ◽  
Tumor Mutational Burden

Immunotherapy as a treatment for cancer is a growing field of endeavor but reports of success have been limited for epithelial ovarian cancer. Overcoming the challenges to developing more effective therapeutic approaches lies in a better understanding of the factors in cancer cells and the surrounding tumor microenvironment that limit response to immunotherapies. This article provides an overview of some ovarian cancer cell features such as tumor-associated antigens, ovarian cancer-derived exosomes, tumor mutational burden and overexpression of immunoinhibitory molecules. Moreover, we describe relevant cell types found in epithelial ovarian tumors including immune cells (T and B lymphocytes, Tregs, NK cells, TAMs, MDSCs) and other components found in the tumor microenvironment including fibroblasts and the adipocytes in the omentum. We focus on how those components may influence responses to standard treatments or immunotherapies.

scholarly journals Epigenetic therapy activates type I interferon signaling in murine ovarian cancer to reduce immunosuppression and tumor burden

2017 ◽  
Vol 114 (51) ◽  
pp. E10981-E10990 ◽  
Author(s):  
Meredith L. Stone ◽  
Katherine B. Chiappinelli ◽  
Huili Li ◽  
Lauren M. Murphy ◽  
Meghan E. Travers ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Histone Deacetylase Inhibitors ◽  
Unmet Need ◽  
Tumor Burden ◽  
Epigenetic Therapy ◽  
Type I ◽  
Type I Ifn

Ovarian cancer is the most lethal of all gynecological cancers, and there is an urgent unmet need to develop new therapies. Epithelial ovarian cancer (EOC) is characterized by an immune suppressive microenvironment, and response of ovarian cancers to immune therapies has thus far been disappointing. We now find, in a mouse model of EOC, that clinically relevant doses of DNA methyltransferase and histone deacetylase inhibitors (DNMTi and HDACi, respectively) reduce the immune suppressive microenvironment through type I IFN signaling and improve response to immune checkpoint therapy. These data indicate that the type I IFN response is required for effective in vivo antitumorigenic actions of the DNMTi 5-azacytidine (AZA). Through type I IFN signaling, AZA increases the numbers of CD45+ immune cells and the percentage of active CD8+ T and natural killer (NK) cells in the tumor microenvironment, while reducing tumor burden and extending survival. AZA also increases viral defense gene expression in both tumor and immune cells, and reduces the percentage of macrophages and myeloid-derived suppressor cells in the tumor microenvironment. The addition of an HDACi to AZA enhances the modulation of the immune microenvironment, specifically increasing T and NK cell activation and reducing macrophages over AZA treatment alone, while further increasing the survival of the mice. Finally, a triple combination of DNMTi/HDACi plus the immune checkpoint inhibitor α-PD-1 provides the best antitumor effect and longest overall survival, and may be an attractive candidate for future clinical trials in ovarian cancer.

Immune cells of the epithelial ovarian cancer microenvironment

2021 ◽  
pp. 67-78
Author(s):  
Varvara Nikolaevna Zhurman ◽  
Natalia Gennadevna Plekhova ◽  
Ekaterina Valeryevna Eliseeva
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Immune Cells ◽  
Ovarian Tumor ◽  
Biologically Active ◽  
Cancer Microenvironment ◽  
Review Of The Literature ◽  
Prognostic Role ◽  
Active Substances

The article is a review of the literature, which analyzes the data on the role of cells of the immune system, cytokines and other biologically active substances secreted by them in the interstitial space of an ovarian tumor. The emphasis is made on the mechanism of realization by immune cells of the stimulating and suppressing action on the development of the tumor. Considerable attention is paid to the prognostic role of immune cells in the development of epithelial ovarian cancer.

scholarly journals The Crowded Crosstalk between Cancer Cells and Stromal Microenvironment in Gynecological Malignancies: Biological Pathways and Therapeutic Implication

2019 ◽  
Vol 20 (10) ◽  
pp. 2401 ◽  
Author(s):  
Rosalba De Nola ◽  
Alessio Menga ◽  
Alessandra Castegna ◽  
Vera Loizzi ◽  
Girolamo Ranieri ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cervical Cancer ◽  
Tumor Microenvironment ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
T Regulatory Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Estrogen Receptor Α ◽  
Biological Pathways ◽  
Cell Subpopulation

The tumor microenvironment plays a pillar role in the progression and the distance dissemination of cancer cells in the main malignancies affecting women—epithelial ovarian cancer, endometrial cancer and cervical cancer. Their milieu acquires specific properties thanks to intense crosstalk between stromal and cancer cells, leading to a vicious circle. Fibroblasts, pericytes, lymphocytes and tumor associated-macrophages orchestrate most of the biological pathways. In epithelial ovarian cancer, high rates of activated pericytes determine a poorer prognosis, defining a common signature promoting ovarian cancer proliferation, local invasion and distant spread. Mesenchymal cells also release chemokines and cytokines under hormonal influence, such as estrogens that drive most of the endometrial cancers. Interestingly, the architecture of the cervical cancer milieu is shaped by the synergy of high-risk Human Papilloma Virus oncoproteins and the activity of stromal estrogen receptor α. Lymphocytes represent a shield against cancer cells but some cell subpopulation could lead to immunosuppression, tumor growth and dissemination. Cytotoxic tumor infiltrating lymphocytes can be eluded by over-adapted cancer cells in a scenario of immune-tolerance driven by T-regulatory cells. Therefore, the tumor microenvironment has a high translational potential offering many targets for biological and immunological therapies.

scholarly journals Immune Checkpoint Inhibitors in Epithelial Ovarian Cancer: An Overview on Efficacy and Future Perspectives

Diagnostics ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 146 ◽  
Author(s):  
Fulvio Borella ◽  
Eleonora Ghisoni ◽  
Gaia Giannone ◽  
Stefano Cosma ◽  
Chiara Benedetto ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Therapeutic Approaches ◽  
Medical Treatments ◽  
New Therapeutic Approaches ◽  
Early Phase Trials ◽  
Improve Patient

Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological cancers. Despite improvements in medical treatments, the prognosis for EOC remains poor, and there is an urgent need for new therapeutic strategies. Immune checkpoint inhibitors (CPIs) have dramatically improved survival of several cancers and are under evaluation in OC. Unfortunately, CPIs have shown globally unsatisfactory results. The aim of this manuscript is to critically review the results from early-phase trials with CPIs in terms of safety and activity, discuss the possible reasons for disappointing results and the new therapeutic approaches to improve patient outcomes.

scholarly journals 2336 Novel PGF2a synthesis pathway in epithelial ovarian cancer

2018 ◽  
Vol 2 (S1) ◽  
pp. 22-22
Author(s):  
Muhan Hu ◽  
Ekta Tiwary ◽  
Rebecca Arend ◽  
Michael Miller
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cell Line ◽  
Cancer Cell Line ◽  
High Grade ◽  
Epithelial Ovarian Cancer Cell ◽  
Main Mode ◽  
Study Population

OBJECTIVES/SPECIFIC AIMS: To understand the role of PGF2a and to characterize a novel cyclooxyrgenase (COX)-independent prostaglandin synthesis pathway in epithelial ovarian cancer. METHODS/STUDY POPULATION: We used high grade epithelial ovarian cancer cell line (OVCAR3) as a model to study our pathway. Our main mode of PGF2a detection is through mass spectrometry. RESULTS/ANTICIPATED RESULTS: Our current results suggest the OVCAR3 cells may synthesize PGF2a independently of COX enzymes. We anticipate this novel pathway may be dependent on the TGFb pathway. DISCUSSION/SIGNIFICANCE OF IMPACT: Understanding the role and synthesis pathway of PGF2a may allow us to uncover a novel therapeutic pathway for high grade ovarian cancer.

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