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Review
. 2023 Apr 11;40(5):142.
doi: 10.1007/s12032-023-01987-x.

Revisiting macrophages in ovarian cancer microenvironment: development, function and interaction

Amr Ahmed El-Arabey  1 , Samia S Alkhalil  2 , Samia T Al-Shouli  3 , Maaweya E Awadalla  4 , Heba W Alhamdi  5 , Taghreed N Almanaa  6 , Samah Saif Eldin M Mohamed  7 , Mohnad Abdalla  8
Affiliations
Review

Revisiting macrophages in ovarian cancer microenvironment: development, function and interaction

Amr Ahmed El-Arabey et al. Med Oncol. .

Abstract

Tumor-associated macrophages (TAMs) are an important component of the tumor microenvironment (TME) and have been linked to immunosuppression and poor prognosis. TAMs have been shown to be harmful in ovarian cancer (OC), with a positive correlation between their high levels of tumors and poor overall patient survival. These cells are crucial in the progression and chemoresistance of OC. The primary pro-tumoral role of TAMs is the release of cytokines, chemokines, enzymes, and exosomes that directly enhance the invasion potential and chemoresistance of OC by activating their pro-survival signalling pathways. TAMs play a crucial role in the metastasis of OC in the peritoneum and ascities by assisting in spheroid formation and cancer cell adhesion to the metastatic regions. Furthermore, TAMs interact with tumor protein p53 (TP53), exosomes, and other immune cells, such as stem cells and cancer-associated fibroblasts (CAFs) to support the progression and metastasis of OC. In this review we revisit development, functions and interactions of TAMs in the TME of OC patients to highlight and shed light on challenges and excitement down the road.

Keywords: Cancer associated fibroblasts; Exosome; Ovarian cancer; Stem cells; TAMs; TP53.

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Conflict of interest statement

The authors declare no conflict of interest for this article.

Figures

Fig. 1
Fig. 1
Estimated number of new cases in 2020, OC all ages: Incidence of ovarian cancer: age-standard rate (ASR) World per 100,000: (Data source: GLOBOCAN 2020; Graph production: international agency for research on cancer {IARC}-world health organization (WHO). The prevalence of OC varies greatly across the world. Eastern Asia, South Central Asia, and Central and Eastern Europe have the greatest incidence rates. Chart created with meta-chart.com
Fig. 2
Fig. 2
Sources of macrophages in ovarian cancer (OC): (1) Tumor-associated macrophages (TAMs) are derived from tissue-resident macrophages, which are primarily derived from the yolk sac during development, or (2) from bone marrow through monocyte differentiation. TAMs are also polarized into anti-tumorigenic M1 or pro-tumorigenic M2 phenotypes in response to tumor microenvironment (TME) of OC signals. Figure created with BioRender.com
Fig. 3
Fig. 3
Recruitment of Tumor-associated macrophages (TAMs) into ovarian cancer (OC): OC cells produce a variety of factors (CCL2, IL-6, CSF-1, NF-κB and MIF) that attract immunosuppressive TAMs into the tumor. In addition, TAMs stimulate OC proliferation, invasion, and angiogenesis by a variety of ways dependent on TAMs marker. Figure created with BioRender.com
Fig. 4
Fig. 4
Tumor-associated macrophages (TAMs)interactions: TAMs interact with mutant TP53 of high-grade serous ovarian cancer (HGSOC) to improve the infiltration of TAMs. GATA3 was also abundantly released from TAMs via exosomes, leading to HGSOC development, angiogenesis, chemo-resistance, and metastasis. TAMs collaborate with cancer-associated fibroblasts (CAFs) to promote HGSOC development and metastasis via the GATA3-HIF-1α axis
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References

    1. Puttabyatappa M, Padmanabhan V. 2018 Developmental programming of ovarian functions and dysfunctions. Vitam Horm Academic Press Inc107 377 422 - PMC - PubMed
    1. Kurman RJ, Shih I-M. Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer–shifting the paradigm. Hum Pathol. 2011;42:918–931. doi: 10.1016/j.humpath.2011.03.003. - DOI - PMC - PubMed
    1. Matulonis UA, Sood AK, Fallowfield L, Howitt BE, Sehouli J, Karlan BY. Ovarian cancer. Nat Rev Dis Primers. 2016;2(1):16061. doi: 10.1038/nrdp.2016.61. - DOI - PMC - PubMed
    1. Berns EMJJ, Bowtell DD. The changing view of high-grade serous ovarian cancer. Cancer Res. 2012;72:2701–2704. doi: 10.1158/0008-5472.CAN-11-3911. - DOI - PubMed
    1. Veras E, Mao T-L, Ayhan A, Ueda S, Lai H, Hayran M, et al. Cystic and adenofibromatous clear cell carcinomas of the ovary: distinctive tumors that differ in their pathogenesis and behavior: a clinicopathologic analysis of 122 cases. Am J Surg Pathol. 2009;33:844–853. doi: 10.1097/PAS.0b013e31819c4271. - DOI - PubMed