Tumor-Associated Macrophages and Myeloid-Derived Suppressor Cells as Immunosuppressive Mechanism in Ovarian Cancer Patients: Progress and Challenges

Okła, Karolina; Wertel, Iwona; Polak, Grzegorz; Surówka, Justyna; Wawruszak, Anna; Kotarski, Jan

doi:10.1080/08830185.2016.1206097

Cited by 28 publications

(33 citation statements)

References 127 publications

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“…These include T cells expressing cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), glucocorticoid-induced TNF receptor family-related protein (GITR), or CD8 + CD28 -Tregs, exhausted CD8 + T cells expressing immune checkpoint inhibitory molecules programmed cell death-1 (PD-1) or lymphocyte activation gene-3 (LAG-3, CD223) [165,166]. In addition, most ovarian tumours overexpress PD-L1 and indolamine 2,3-dioxygenase (IDO1) and/or secrete cytokines like VEGF and TGFβ which enhances the proliferation of regulatory cells (Tregs) and facilitate their action thus promoting T cell suppressive microenvironment and functional exhaustion [167,168]. In addition, downregulation or loss of expression of major histocompatibility complexes (MHC)-I and II on the tumour cells leads to decreased cytotoxic T lymphocyte action [169].…”

Section: Immunotherapymentioning

confidence: 99%

Ovarian Cancer, Cancer Stem Cells and Current Treatment Strategies: A Potential Role of Magmas in the Current Treatment Methods

Ahmed

Kadife²,

Raza

et al. 2020

Cells

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Epithelial ovarian cancer (EOC) constitutes 90% of ovarian cancers (OC) and is the eighth most common cause of cancer-related death in women. The cancer histologically and genetically is very complex having a high degree of tumour heterogeneity. The pathogenic variability in OC causes significant impediments in effectively treating patients, resulting in a dismal prognosis. Disease progression is predominantly influenced by the peritoneal tumour microenvironment rather than properties of the tumor and is the major contributor to prognosis. Standard treatment of OC patients consists of debulking surgery, followed by chemotherapy, which in most cases end in recurrent chemoresistant disease. This review discusses the different origins of high-grade serous ovarian cancer (HGSOC), the major sub-type of EOC. Tumour heterogeneity, genetic/epigenetic changes, and cancer stem cells (CSC) in facilitating HGSOC progression and their contribution in the circumvention of therapy treatments are included. Several new treatment strategies are discussed including our preliminary proof of concept study describing the role of mitochondria-associated granulocyte macrophage colony-stimulating factor signaling protein (Magmas) in HGSOC and its unique potential role in chemotherapy-resistant disease. of 35have been observed in OC patients but not in patients with benign and borderline tumours, and this hypomethylation correlates with advanced-stage disease and poor prognosis [48,49]. A genome-wide methylation profiling of blood cells from healthy controls and age-matched untreated OC patients identified CpG methylation of 2714 cancer-related genes, of which 56% were hypomethylated [50]. Ovarian Cancer Stem CellsCellular heterogeneity associated with genetic and epigenetic changes in tumours are linked with the initiation and expansion of CSCs, a population of cells within the tumour, which initiate tumour growth through self-renewal and differentiation processes [51,52]. These cells are more adaptive to the changing tumour microenvironment and tend to be more resistant to treatment. CSCs are highly plastic and a few numbers of isolated CSCs have been shown to be responsible for tumorgenesis and are more chemotherapy and radiation resistant due to their dormant state and a high expression of drug efflux pumps [53,54]. As a result, CSCs are able to adapt to different tumour microenvironments and survive due to their efficient DNA repair mechanisms and their capacity to evade host immune surveillance [55][56][57]. These inherent properties of CSCs suggest an active role in tumour relapse and emphasize the need to develop effective targeted therapies to improve clinical outcomes in patients [51][52][53][54][55][56][57].Stem cells have been identified in ovaries and fallopian tubes [58,59]. These cells express proteins including aldehyde dehydrogenase family 1 A2 (ALDH1A2), homeobox protein NANOG, LIM homeobox protein 9 (LHX9) and frizzled-related protein 1 (SRFP1) and have been observed in OSE, CIC and fimbria [2,[58][59][60][61][62]. In a...

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Section: Immunotherapymentioning

confidence: 99%

Ovarian Cancer, Cancer Stem Cells and Current Treatment Strategies: A Potential Role of Magmas in the Current Treatment Methods

Ahmed

Kadife²,

Raza

et al. 2020

Cells

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“…Tumor-associated macrophages (TAMS) are the major subpopulation of this lineage cells in the ovarian TME. TAMS can readily change phenotype and function in the presence of soluble molecules in the surrounding milieu [ 56 , 57 ]. These cells can be recruited from blood monocytes, or arise from resident peritoneal macrophages [ 54 , 58 , 59 , 60 ].…”

Section: Multifaceted Nature Of Macrophages In the Tmementioning

confidence: 99%

Regulation of Ovarian Cancer Prognosis by Immune Cells in the Tumor Microenvironment

Drakes

Stiff

2018

Cancers

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It is estimated that in the United States in 2018 there will be 22,240 new cases of ovarian cancer and 14,070 deaths due to this malignancy. The most common subgroup of this disease is high-grade serous ovarian cancer (HGSOC), which is known for its aggressiveness, high recurrence rate, metastasis to other sites, and the development of resistance to conventional therapy. It is important to understand the ovarian cancer tumor microenvironment (TME) from the viewpoint of the function of pre-existing immune cells, as immunocompetent cells are crucial to mounting robust antitumor responses to prevent visible tumor lesions, disease progression, or recurrence. Networks consisting of innate and adaptive immune cells, metabolic pathways, intracellular signaling molecules, and a vast array of soluble factors, shape the pathogenic nature of the TME and are useful prognostic indicators of responses to conventional therapy and immunotherapy, and subsequent survival rates. This review highlights key immune cells and soluble molecules in the TME of ovarian cancer, which are important in the development of effective antitumor immunity, as well as those that impair effector T cell activity. A more insightful knowledge of the HGSOC TME will reveal potential immune biomarkers to aid in the early detection of this disease, as well as biomarkers that may be targeted to advance the design of novel therapies that induce potent antitumor immunity and survival benefit.

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“…This treatment significantly prolonged survival, highlighting the need for more immunotherapies targeting innate immunity within the TME [ 49 ]. However, there are still many unknowns concerning the different MDSC phenotypes and levels in tumor tissue, peripheral blood, and/or ascites fluid, and how their presence influences the TME [ 50 ].…”

Section: Strategies Targeting Immunosuppression In the Tmementioning

confidence: 99%

Ovarian Cancer Immunotherapy: Preclinical Models and Emerging Therapeutics

McCloskey

Rodriguez

Galpin

et al. 2018

Cancers

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Immunotherapy has emerged as one of the most promising approaches for ovarian cancer treatment. The tumor microenvironment (TME) is a key factor to consider when stimulating antitumoral responses as it consists largely of tumor promoting immunosuppressive cell types that attenuate antitumor immunity. As our understanding of the determinants of the TME composition grows, we have begun to appreciate the need to address both inter- and intra-tumor heterogeneity, mutation/neoantigen burden, immune landscape, and stromal cell contributions. The majority of immunotherapy studies in ovarian cancer have been performed using the well-characterized murine ID8 ovarian carcinoma model. Numerous other animal models of ovarian cancer exist, but have been underutilized because of their narrow initial characterizations in this context. Here, we describe animal models that may be untapped resources for the immunotherapy field because of their shared genomic alterations and histopathology with human ovarian cancer. We also shed light on the strengths and limitations of these models, and the knowledge gaps that need to be addressed to enhance the utility of preclinical models for testing novel immunotherapeutic approaches.

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Tumor-Associated Macrophages and Myeloid-Derived Suppressor Cells as Immunosuppressive Mechanism in Ovarian Cancer Patients: Progress and Challenges

Cited by 28 publications

References 127 publications

Ovarian Cancer, Cancer Stem Cells and Current Treatment Strategies: A Potential Role of Magmas in the Current Treatment Methods

Ovarian Cancer, Cancer Stem Cells and Current Treatment Strategies: A Potential Role of Magmas in the Current Treatment Methods

Regulation of Ovarian Cancer Prognosis by Immune Cells in the Tumor Microenvironment

Ovarian Cancer Immunotherapy: Preclinical Models and Emerging Therapeutics

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