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

Gupta, Vijayalaxmi; Yull, Fiona E.; Khabele, Dineo

doi:10.3390/cancers10100366

Cited by 76 publications

(77 citation statements)

References 76 publications

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“…Ascite, which is a hallmark of OC, contains a large number of components of unique peritoneal TME, including tumor spheroids and immune cells, such as TAMs and T cells (201,202). Experimental mouse models have demonstrated that TAMs constitute a major cell fraction in ascites that support the survival of cancer cells and promote cancer progression, chemoresistance, and immunosuppression (202,204,(221)(222)(223).…”

Section: Ascitic Tams In Metastasis Of Ovarian Cancermentioning

confidence: 99%

Tumor-Associated Macrophages in Human Breast, Colorectal, Lung, Ovarian and Prostate Cancers

et al. 2020

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Tumor-associated macrophages (TAMs) are major innate immune cells that constitute up to 50% of the cell mass of human tumors. TAMs are highly heterogeneous cells that originate from resident tissue-specific macrophages and from newly recruited monocytes. TAMs' variability strongly depends on cancer type, stage, and intratumor heterogeneity. Majority of TAMs are programmed by tumor microenvironment to support primary tumor growth and metastatic spread. However, TAMs can also restrict tumor growth and metastasis. In this review, we summarized the knowledge about the role of TAMs in tumor growth, metastasis and in the response to cancer therapy in patients with five aggressive types of cancer: breast, colorectal, lung, ovarian, and prostate cancers that are frequently metastasize into distant organs resulting in high mortality of the patients. Two major TAM parameters are applied for the evaluation of TAM correlation with the cancer progression: total amount of TAMs and specific phenotype of TAMs identified by functional biomarkers. We summarized the data generated in the wide range of international patient cohorts on the correlation of TAMs with clinical and pathological parameters of tumor progression including lymphatic and hematogenous metastasis, recurrence, survival, therapy efficiency. We described currently available biomarkers for TAMs that can be measured in patients' samples (tumor tissue and blood). CD68 is the major biomarker for the quantification of total TAM amounts, while transmembrane receptors (stabilin-1, CD163, CD206, CD204, MARCO) and secreted chitinase-like proteins (YKL-39, YKL-40) are used as biomarkers for the functional TAM polarization. We also considered that specific role of TAMs in tumor progression can depend on the localization in the intratumoral compartments. We have made the conclusion for the role of TAMs in primary tumor growth, metastasis, and therapy sensitivity for breast, colorectal, lung, ovarian, and prostate cancers. In contrast to other cancer types, majority of clinical studies indicate that TAMs in colorectal cancer have protective role for the patient and interfere with primary tumor growth

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Section: Ascitic Tams In Metastasis Of Ovarian Cancermentioning

confidence: 99%

Tumor-Associated Macrophages in Human Breast, Colorectal, Lung, Ovarian and Prostate Cancers

et al. 2020

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“…110 Metastatic ovarian cancer is characterized by ascites and tumor implants in the peritoneal cavity. 111 Unfortunately, results of several single-agent CBT clinical trials in ovarian cancer are discouraging, with objective response rates of 6%-15%. 7 As a result, there are no FDA-approved checkpoint inhibitors for ovarian cancer beyond the use of anti-PD-1 (pembrolizumab) for microsatellite instability-high tumors.…”

Section: Myeloid Apc In Cbt-resistant Carcinomas Invasive Breast Carcmentioning

confidence: 99%

“…128 They are highly plastic and depending on the cytokines and growth factors present in the TME, they can be skewed toward an inflammatory M1-like state or an immunosuppressive M2-like state. 111 Studies have shown that high amounts of CSF1 secreted by ovarian cancer cells can cause PM to differentiate into CD206 + M2 TAM. 129 The resulting increase in the M2/M1 phenotype ratio of TAM has been shown to correlate with decreased survival in patients with ovarian cancer.…”

Section: Myeloid Apc In Cbt-resistant Carcinomas Invasive Breast Carcmentioning

confidence: 99%

Impact of anatomic site on antigen-presenting cells in cancer

Zagorulya

Duong

Spranger

2020

J Immunother Cancer

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Checkpoint blockade immunotherapy (CBT) can induce long-term clinical benefits in patients with advanced cancer; however, response rates to CBT vary by cancer type. Cancers of the skin, lung, and kidney are largely responsive to CBT, while cancers of the pancreas, ovary, breast, and metastatic lesions to the liver respond poorly. The impact of tissue-resident immune cells on antitumor immunity is an emerging area of investigation. Recent evidence indicates that antitumor immune responses and efficacy of CBT depend on the tissue site of the tumor lesion. As myeloid cells are predominantly tissue-resident and can shape tumor-reactive T cell responses, it is conceivable that tissue-specific differences in their function underlie the tissue-site-dependent variability in CBT responses. Understanding the roles of tissue-specific myeloid cells in antitumor immunity can open new avenues for treatment design. In this review, we discuss the roles of tissue-specific antigen-presenting cells (APCs) in governing antitumor immune responses, with a particular focus on the contributions of tissue-specific dendritic cells. Using the framework of the Cancer-Immunity Cycle, we examine the contributions of tissue-specific APC in CBT-sensitive and CBT-resistant carcinomas, highlight how these cells can be therapeutically modulated, and identify gaps in knowledge that remain to be addressed.

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“…For example, miR-21-3p, miR-125b-5p, and miR-181d-5p are highly expressed in exosomes derived from EOC, which are involved in M2 polarization of macrophages in hypoxic conditions [30]. Macrophages modified by exosomes promote the proliferation and migration of EOC [31]. The expression and function of exosomal miR-214-3p identified in this study suggest that miR-214-3p may contribute to the oncogenic effects of exosomes by affecting other cell types in the tumor microenvironment of EOC.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of miR-214-3p Aids in Preventing Epithelial Ovarian Cancer Malignancy by Increasing the Expression of LHX6

Yang

Kim

Park

et al. 2019

Cancers

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In human epithelial ovarian cancer (EOC), various miRNAs can function as either oncogenes or tumor suppressor genes. We investigated miRNAs known to be involved in EOC progression and analyzed their expression in tissues and serum-derived exosomes from benign serous cystadenoma, borderline serous tumor, low-grade serous ovarian cancer, and high-grade serous ovarian cancer patients (HGSO). The HGSO group was divided based on the platinum-free interval, which is defined as the duration from the completion of platinum-based chemotherapy to recurrence. We also analyzed the mRNA levels of target genes that candidate miRNAs might regulate in patient tissues. miR-214-3p was highly expressed in tissues and exosomes derived from EOC with high malignancy and also found to regulate the expression of LIM homeobox domain 6 (LHX6) mRNA. Serum exosomal levels of miR-214-3p were significantly increased in platinum-resistant HGSO (25.2-fold, p < 0.001) compared to the exosomal expression of benign tumor patients. On transfection of miR-214-3p inhibitor in EOC cells, cell proliferation was inhibited while apoptotic cell death was increased. Collectively, we suggest that miR-214-3p in serum exosomes can be a potential biomarker for the diagnosis and prognosis of ovarian tumor, and its inhibition can be a supportive treatment for EOC.

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

Cited by 76 publications

References 76 publications

Tumor-Associated Macrophages in Human Breast, Colorectal, Lung, Ovarian and Prostate Cancers

Tumor-Associated Macrophages in Human Breast, Colorectal, Lung, Ovarian and Prostate Cancers

Impact of anatomic site on antigen-presenting cells in cancer

Inhibition of miR-214-3p Aids in Preventing Epithelial Ovarian Cancer Malignancy by Increasing the Expression of LHX6

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