Immunosuppressive tumor microenvironment and uterine fibroids: Role in collagen synthesis

Eslam E Saad; Rachel Michel; Mostafa A Borahay

doi:10.1016/j.cytogfr.2023.10.002

Immunosuppressive tumor microenvironment and uterine fibroids: Role in collagen synthesis

Cytokine Growth Factor Rev. 2024 Feb:75:93-100. doi: 10.1016/j.cytogfr.2023.10.002. Epub 2023 Oct 6.

Authors

Eslam E Saad¹, Rachel Michel², Mostafa A Borahay³

Affiliations

¹ Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
² Department of Population, Family, and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, MD 21205, USA.
³ Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: mboraha1@jhmi.edu.

PMID: 37839993
PMCID: PMC10922281 (available on 2025-02-01)
DOI: 10.1016/j.cytogfr.2023.10.002

Abstract

Uterine fibroids (UF), also called uterine leiomyoma, is one of the most prevalent uterine tumors. UF represents a serious women's health global problem with a significant physical, emotional, and socioeconomic impact. Risk factors for UF include racial disparities, age, race, hormonal factors, obesity, and lifestyle (diet, physical activity, and stress. There are several biological contributors to UF pathogenesis such as cellular proliferation, angiogenesis, and extracellular matrix (ECM) accumulation. This review addresses tumor immune microenvironment as a novel mediator of ECM deposition. Polarization of immune microenvironment towards the immunosuppressive phenotype has been associated with ECM deposition. Immunosuppressive cells include M2 macrophage, myeloid-derived suppressor cells (MDSCs), and Th17 cells, and their secretomes include interleukin 4 (IL-4), IL-10, IL-13, IL-17, IL-22, arginase 1, and transforming growth factor-beta (TGF-β1). The change in the immune microenvironment not only increase tumor growth but also aids in collagen synthesis and ECM disposition, which is one of the main hallmarks of UF pathogenesis. This review invites further investigations on the change in the UF immune microenvironment as well as a novel targeting approach instead of the traditional UF hormonal and supportive treatment.

Keywords: ECM; M2 Macrophage; MDSCs; TH17; Uterine Fibroids.

Publication types

Review
Research Support, N.I.H., Extramural

MeSH terms

Collagen
Extracellular Matrix
Female
Humans
Leiomyoma* / pathology
Leiomyoma* / therapy
Tumor Microenvironment
Uterine Neoplasms* / pathology
Uterine Neoplasms* / therapy

Substances

Collagen

Grants and funding

R01 HD094380/HD/NICHD NIH HHS/United States