Role of tumor microenvironment in the pathobiology of ovarian cancer: Insights and therapeutic opportunities

Ghoneum, Alia; Afify, Hesham; Salih, Ziyan; Kelly, Michael G.; Said, Neveen

doi:10.1002/cam4.1741

Cited by 45 publications

(41 citation statements)

References 101 publications

(225 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A remarkable example of direct contacts between the stromal (the fibroblasts and the mesothelial cells) and the cancer cells can be seen in spheroids of the ovarian carcinoma ascites [107][108][109][110]. When in the abdominal cavity, tumor cells combine with the free-floating myofibroblast cells forming multicellular heterotypic spheroids.…”

Section: Circulating Cancer Cells Form Clusters Through Tomo-and Hetementioning

confidence: 99%

Are Synapse-Like Structures a Possible Way for Crosstalk of Cancer with Its Microenvironment?

Alekseenko

Чернов

Kostrov

2020

Cancers

View full text Add to dashboard Cite

The failure of therapies directed at targets within cancer cells highlight the necessity for a paradigm change in cancer therapy. The attention of researchers has shifted towards the disruption of cancer cell interactions with the tumor microenvironment. A typical example of such a disruption is the immune checkpoint cancer therapy that disrupts interactions between the immune and the cancer cells. The interaction of cancer antigens with T cells occurs in the immunological synapses. This is characterized by several special features, i.e., the proximity of the immune cells and their target cells, strong intercellular adhesion, and secretion of signaling cytokines into the intercellular cleft. Earlier, we hypothesized that the cancer-associated fibroblasts interacting with cancer cells through a synapse-like adhesion might play an important role in cancer tumors. Studies of the interactions between cancer cells and cancer-associated fibroblasts showed that their clusterization on the membrane surface determined their strength and specificity. The hundreds of interacting pairs are involved in the binding that may indicate the formation of synapse-like structures. These interactions may be responsible for successful metastasis of cancer cells, and their identification and disruption may open new therapeutic possibilities.

show abstract

Section: Circulating Cancer Cells Form Clusters Through Tomo-and Hetementioning

confidence: 99%

Are Synapse-Like Structures a Possible Way for Crosstalk of Cancer with Its Microenvironment?

Alekseenko

Чернов

Kostrov

2020

Cancers

View full text Add to dashboard Cite

show abstract

“…However, not all patients are candidates for upfront surgery [6]. Furthermore, optimal debunking surgery has been shown to enhance patient survival, compared to sub-optimal debunking, due to the microscopic spread of inaccessible lesions throughout the abdomen [7]. Although the standard treatment results in a complete response rate of 40-60%, more than 90% of patients relapse within 18 months and ultimately die from the disease.…”

Section: Introductionmentioning

confidence: 99%

Photodynamic Therapy Using a New Folate Receptor-Targeted Photosensitizer on Peritoneal Ovarian Cancer Cells Induces the Release of Extracellular Vesicles with Immunoactivating Properties

Baydoun

Moralès

Frochot

et al. 2020

JCM

View full text Add to dashboard Cite

Often discovered at an advanced stage, ovarian cancer progresses to peritoneal carcinoma, which corresponds to the invasion of the serosa by multiple tumor implants. The current treatment is based on the combination of chemotherapy and tumor cytoreduction surgery. Despite the progress and standardization of surgical techniques combined with effective chemotherapy, post-treatment recurrences affect more than 60% of women in remission. Photodynamic therapy (PDT) has been particularly indicated for the treatment of superficial lesions on large surfaces and appears to be a relevant candidate for the treatment of microscopic intraperitoneal lesions and non-visible lesions. However, the impact of this therapy on immune cells remains unclear. Hence, the objective of this study is to validate the efficacy of a new photosensitizer [pyropheophorbide a-polyethylene glycol-folic acid (PS)] on human ovarian cancer cells and to assess the impact of the secretome of PDT-treated cells on human peripheral blood mononuclear cells (PBMC). We show that PS, upon illumination, can induce cell death of different ovarian tumor cells. Furthermore, PDT using this new PS seems to favor activation of the immune response by inducing the secretion of effective cytokines and inhibiting the pro-inflammatory and immunosuppressive ones, as well as releasing extracellular vesicles (EVs) prone to activating immune cells. Finally, we show that PDT can activate CD4+ and CD8+ T cells, resulting in a potential immunostimulating process. The results of this pilot study therefore indicate that PS-PDT treatment may not only be effective in rapidly and directly destroying target tumor cells but also promote the activation of an effective immune response; notably, by EVs. These data thus open up good prospects for the treatment of micrometastases of intraperitoneal ovarian carcinosis which are currently inoperable.

show abstract

“…Ovarian cancer metastasizes very early in the disease process. Malignant cells shed from the primary tumour, survive anchorage-independent apoptosis as free-floating cells or form spheroids, and spread throughout the peritoneal cavity to proliferate and interact with mesothelial cells and adipocytes of the omentum [ 71 , 72 ]. Ovarian cancer cells preferentially home to “milky spots” of the peritoneum [ 73 ], aggregates of immune cells, including macrophages, lymphocytes, and plasma cells supplied by blood and lymphatic vessels, which function as secondary lymphoid organs and promote immunity to peritoneal antigens [ 74 ].…”

Section: Tumour Microenvironment (Tme) Of Solid Cancers Including mentioning

confidence: 99%

“…TILs include CD8+ T-cells, Tregs, regulatory B-cells (Bregs), type II NK T-cells (which recognise lipid antigens and are not the same as NK cells), and Th2 CD4+ cells which upregulate B-cell responses, play roles in remodeling and may or may not promote tumour growth [ 68 , 71 ]. They can mediate immune editing of cancer cell by processes of elimination, equilibrium and escape [ 89 ].…”

Section: Tumour Microenvironment (Tme) Of Solid Cancers Including mentioning

confidence: 99%

Epithelial Ovarian Cancer and the Immune System: Biology, Interactions, Challenges and Potential Advances for Immunotherapy

Macpherson

Barry

Ricciardelli

et al. 2020

JCM

View full text Add to dashboard Cite

Recent advances in the understanding of immune function and the interactions with tumour cells have led to the development of various cancer immunotherapies and strategies for specific cancer types. However, despite some stunning successes with some malignancies such as melanomas and lung cancer, most patients receive little or no benefit from immunotherapy, which has been attributed to the tumour microenvironment and immune evasion. Although the US Food and Drug Administration have approved immunotherapies for some cancers, to date, only the anti-angiogenic antibody bevacizumab is approved for the treatment of epithelial ovarian cancer. Immunotherapeutic strategies for ovarian cancer are still under development and being tested in numerous clinical trials. A detailed understanding of the interactions between cancer and the immune system is vital for optimisation of immunotherapies either alone or when combined with chemotherapy and other therapies. This article, in two main parts, provides an overview of: (1) components of the normal immune system and current knowledge regarding tumour immunology, biology and their interactions; (2) strategies, and targets, together with challenges and potential innovative approaches for cancer immunotherapy, with attention given to epithelial ovarian cancer.

show abstract

Role of tumor microenvironment in the pathobiology of ovarian cancer: Insights and therapeutic opportunities

Cited by 45 publications

References 101 publications

Are Synapse-Like Structures a Possible Way for Crosstalk of Cancer with Its Microenvironment?

Are Synapse-Like Structures a Possible Way for Crosstalk of Cancer with Its Microenvironment?

Photodynamic Therapy Using a New Folate Receptor-Targeted Photosensitizer on Peritoneal Ovarian Cancer Cells Induces the Release of Extracellular Vesicles with Immunoactivating Properties

Epithelial Ovarian Cancer and the Immune System: Biology, Interactions, Challenges and Potential Advances for Immunotherapy

Contact Info

Product

Resources

About