scholarly journals Interaction between Treg cells and tumor-associated macrophages in the tumor microenvironment of epithelial ovarian cancer

2016 ◽  
Vol 36 (6) ◽  
pp. 3472-3478 ◽  
Author(s):  
Qinyi Zhu ◽  
Xiaoli Wu ◽  
Yueqian Wu ◽  
Xipeng Wang
Keyword(s):  
Ovarian Cancer ◽  
Tumor Microenvironment ◽  
Epithelial Ovarian Cancer ◽  
Treg Cells ◽  
Tumor Associated Macrophages

scholarly journals Bipolar Tumor-Associated Macrophages in Ovarian Cancer as Targets for Therapy

Cancers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 366 ◽  
Author(s):  
Vijayalaxmi Gupta ◽  
Fiona Yull ◽  
Dineo Khabele
Keyword(s):  
Ovarian Cancer ◽  
Tumor Microenvironment ◽  
Epithelial Ovarian Cancer ◽  
Tumor Cells ◽  
Peritoneal Metastasis ◽  
Gynecological Cancer ◽  
Malignant Ascites ◽  
Tumor Associated Macrophages ◽  
Fatal Disease ◽  
Cancer Tumor

Ovarian cancer, a rare but fatal disease, has been a challenging area in the field of gynecological cancer. Ovarian cancer is characterized by peritoneal metastasis, which is facilitated by a cross-talk between tumor cells and other cells in the tumor microenvironment (TME). In epithelial ovarian cancer, tumor-associated macrophages (TAMs) constitute over 50% of cells in the peritoneal TME and malignant ascites, and are potential targets for therapy. Here, we review the bipolar nature of TAMs and the evolving strategies to target TAMs in ovarian cancer.

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 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.

Abstract 1543: Tumor associated macrophages are associated with poor survival in epithelial ovarian cancer.

2013 ◽  
Author(s):  
Wafic El Masri ◽  
Caroline Hillerup ◽  
Charlotte Topka ◽  
Chintda Santiskulvong ◽  
Alexander Chiang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Tumor Associated Macrophages ◽  
Poor Survival

scholarly journals The Association of Peripheral Blood Regulatory T-Cell Concentrations With Epithelial Ovarian Cancer: A Brief Report

2016 ◽  
Vol 27 (1) ◽  
pp. 11-16 ◽  
Author(s):  
Rikki A. Cannioto ◽  
Lara E. Sucheston-Campbell ◽  
Shalaka Hampras ◽  
Ellen L. Goode ◽  
Keith Knutson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Confidence Interval ◽  
Epithelial Ovarian Cancer ◽  
Peripheral Blood ◽  
Odds Ratio ◽  
Treg Cells ◽  
Healthy Controls ◽  
Treg Frequency ◽  
History Of ◽  
History Of Cancer

ObjectiveThere is a mounting body of evidence demonstrating higher percentages of regulatory T (Treg) cells in the peripheral blood of patients with cancer in comparison to healthy controls, but there is a paucity of epidemiological literature characterizing circulating Treg cells among patients with epithelial ovarian cancer (EOC). To investigate the role of peripheral Treg cells in ovarian neoplasms, we conducted a case–control study to characterize circulating concentrations of Treg cells among patients with EOC, women with benign ovarian conditions, and healthy controls without a history of cancer.Materials and MethodsParticipants were identified for inclusion due to their participation in the Data Bank and BioRepository program at Roswell Park Cancer Institute in Buffalo, NY. Patients included 71 women with a primary diagnosis of EOC and 195 women with a diagnosis of benign ovarian conditions. Controls included 101 age- and race-matched women without a history of cancer. Nonfasting, pretreatment peripheral blood levels of CD3+CD4+CD25+FOXP3+ Treg cells were measured using flow cytometric analyses and expressed as a percentage of total CD3+ cells and as a percentage of total CD3+CD4+ cells.ResultsCompared to healthy controls and women with benign ovarian conditions, patients with EOC had significantly higher frequency of Treg cells (P < 0.04). In multivariable logistic regression analyses using Treg frequency expressed as a percentage of CD+3 cells, we observed a significant positive association between Treg cell percentage and EOC risk, with each 1% increase associated with a 37% increased risk of EOC (odds ratio, 1.37; 95% confidence interval, 1.04–1.80). We observed a similar trend when Treg frequency was expressed as a percentage of CD3+CD+4 cells (odds ratio, 1.22; 95% confidence interval, 0.99–1.49).ConclusionsThe current study provides support that peripheral Treg cell frequency is elevated in patients with EOC in comparison to women with benign ovarian conditions and healthy controls.

Targeting myeloid cells in the tumor microenvironment as a strategy to enhance vaccine efficacy in epithelial ovarian cancer

2014 ◽  
Vol 133 ◽  
pp. 113
Author(s):  
N.V. Kolomeyevskaya ◽  
N. Khan ◽  
M. Grimm ◽  
K. Singel ◽  
K.S. Grzankowski ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Microenvironment ◽  
Epithelial Ovarian Cancer ◽  
Vaccine Efficacy ◽  
Myeloid Cells

scholarly journals Tumor-associated macrophages mediate immune suppression by secreting PD-L1+ exosomes in epithelial ovarian cancer

2019 ◽  
Author(s):  
Xingchen Zhou ◽  
Xiaoli Wu ◽  
Xiaoduan Li ◽  
Yi Zhang ◽  
Xipeng Wang
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
T Cell ◽  
Epithelial Ovarian Cancer ◽  
Signaling Pathway ◽  
Immune Suppression ◽  
Ovarian Tumor ◽  
Tumor Associated Macrophages ◽  
Programmed Death ◽  
Benign Ovarian Tumor

Abstract Purpose: To study the role of programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) signaling pathway in patients with epithelial ovarian cancer (EOC). Methods: A total of 10 EOC specimens and 10 benign ovarian tumor were obtained from surgery and the pathological type. We used the methods of immunofluorescence confocal microscopy, western blot, MTT assay, apoptosis detection and co-culture to verify the aim of the research. Results: In the present study, it was validated that the number of PD-L1+ tumor-associated macrophages (TAMs) per field was significantly increased in EOC tissues compared with benign ovarian tumor tissues. Furthermore, it was demonstrated that PD-L1 was expressed on the membrane of TAM-derived exosomes, which may inhibit the proliferation and induce the apoptosis of T cells by activating the caspase 3 signaling pathway. The analysis of the supernatant of T cells co-cultured with TAM drived exosome revealed that the levels of pro-inflammatory cytokines and tumor necrosis factor α decreased compared with those T cells co-cultured with monocyte drived exosome. However, the expression of the immuno-suppressive cytokine, interleukin 10 and markers of T cell exhaustion (the inhibitory molecule lymphocyte activated gene-3, T-cell immunoglobulin and mucin domain-containing protein-3 and PD-1) increased. Conclusions: The present study demonstrated that the M2-derived exosomes regulate immune suppression in the EOC microenvironment. The findings of the present study provide a theoretical basis for future target therapy on exosomes from immune cells to treat EOC.

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