<p>Tumor-Associated Macrophages (TAMs): A Critical Activator In Ovarian Cancer Metastasis</p>

Abstract

Tumor-associated macrophages (TAMs) that appear in every stage of cancer progression are usually tumor-promoting cells and are present abundantly in the tumor-associated microenvironment. In ovarian cancer, the overall and intratumoral M1/M2 ratio is a relatively efficient TAM parameter for predicting the prognosis of patients, especially for serous tissue type cancer. TAMs exhibit immunological checkpoint modulators, such as the B7 family and programmed death-ligand 1 (PD-L1), and play a key role in the development, metastasis and invasion of ovarian cancer, but the underlying mechanism is barely understood. Ovarian cancer is a severe gynecological malignancy with high mortality. Ovarian cancer-associated death can primarily be attributed to cancer metastasis. The majority of patients are diagnosed with wide dissemination in the peritoneum and omentum, limiting the effectiveness of surgery and chemotherapy. In addition, unlike other well-documented cancers, metastasis through vasculature is not a usual dissemination pathway in ovarian cancer. This review sheds light on TAMs and the main process and mechanism of ovarian cancer metastasis.

Neutrophil extracellular trap formation correlates with improved overall survival in ovarian cancer

“…The ascites samples actually do not show an up-regulation of LOX-5-derived products, which have been made responsible for tumor-promoting effects of neutrophils [68], but show increased levels of LOX and COX-products associated with the resolution of inflammation. Microparticles containing 14-HDoHE and 17-HDoHE and shedded from neutrophils may inhibit the pro-inflammatory action of activated macrophages [70], which have been demonstrated to promote tumor growth and metastasis [54]. The present in vitro studies with neutrophils isolated from healthy donors demonstrate that stimulation via NOX or via calcium release causes substantially different effector functions in neutrophils.…”

“…Here, with regard to HGSOC we have collected ample evidence for NETosis associated with non-miliary tumor spread. NETosis as well as the activity of tumor-associated macrophages have been rather linked to the promotion of metastasis [53,54]. While non-miliary tumor spread is indeed characterized by more invasive growth, it is associated with better overall survival.…”

Impact of age-, cancer-, and treatment-driven inflammation on T cell function and immunotherapy

“…However, there are several immunosuppressive mechanisms in the ovarian TME that limit the function of T cells, including T REG cells, MDSCs, and tumor‐associated Mϕs (TAMs) cancer‐associated fibroblasts, endothelial cells, adipocytes and the cancer cells themselves 75–77 ( Figure 2 ). Local inflammation promotes the secretion of prostaglandins that directly inhibit CD8 T cell function in solid cancers 78 .…”

“…Treg cells may inhibit tumor‐specific responses in the ovarian TME using a number of mechanisms, including the production of suppressive cytokines, such as IL‐10 and TGF‐β, that reduce the killing capacity of CD8 T cells. MDSCs and TAMs can also secrete suppressive cytokines and they can suppress T cell activation by engaging the inhibitory molecules 76,77 . Cumulatively, these cells create a local environment of chronic inflammation with high IL‐6 and TNF that inhibit T cell function, 80,81 alongside other suppressive mechanisms.…”

Signaling of Macrophages that Contours the Tumor Microenvironment for Promoting Cancer Development

“…In addition to their role in both innate and adaptive immunity, research has shown that macrophages also play a dynamic role in the body by interacting with immune cells and epithelial cells to regulate the cellular environment through secretion of cytokines and chemokines [1][2][3][4]. Furthermore, studies on various cancers have revealed that macrophages participate in tumor initiation and development, especially the M2 subtype of macrophages [5][6][7][8][9][10]. A comprehensive understanding of macrophage polarization/subtypes and their function in cellular signaling will not only advance our current knowledge on these multifaceted macrophages but also shed light on how to target them for a cancer therapy purpose.…”