Senescence-associated secretory phenotype (SASP) and uterine fibroids: Association with PD-L1 activation and collagen deposition

• Published in: Ageing research reviews 2024-06, Vol.97, p.102314, Article 102314
• Main Authors: Saad, Eslam E., Michel, Rachel, Borahay, Mostafa A.
• Format: Article
• Language: English
• Subjects: Aging - immunology; Aging - metabolism; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Cellular Senescence; Collagen; Collagen - genetics; Collagen - metabolism; Female; Humans; Leiomyoma - genetics; Leiomyoma - metabolism; Leiomyoma - pathology; PD-L1; SASPs; Senescence-Associated Secretory Phenotype; Tumor Microenvironment - immunology; Uterine Fibroids; Uterine Neoplasms - genetics; Uterine Neoplasms - metabolism; Uterine Neoplasms - pathology
• ISSN: 1568-1637; 1872-9649; 1872-9649
• DOI: 10.1016/j.arr.2024.102314

Uterine fibroids (or uterine leiomyoma, UFs) are one of the most prevalent benign uterine tumors with high proliferation and collagen synthesis capabilities. UFs are a significant worldwide health issue for women, affecting their physical and financial well-being. Risk factors for UFs include age, racial disparities, obesity, uterine infections, hormonal variation, and lifestyle (i.e., diet, exercise, stress, and smoking). Senescence and its associated secretory phenotypes (SASPs) are among the most salient changes accompanying the aging process. As a result, SASPs are suggested to be one of the major contributors to developing UFs. Interleukin 6 (IL-6), IL-8, IL-1, chemokine ligand 20 (CCL-20), and transforming growth factor-beta (TGF-β) are the most prominent SASPs associated with aging. In addition, different processes contribute to UFs such as collagen deposition and the changes in the immune microenvironment. Programmed death ligand 1 is a major player in the tumor immune microenvironment, which helps tumor cells evade immune attacks. This review focuses on the correlation of SASPs on two axes of tumor progression: immune suppression and collagen deposition. This review opens the door towards more investigations regarding changes in the UF immune microenvironment and age-UFs correlation and thus, a novel targeting approach for UF treatment. [Display omitted] •SASPs participate in UF pathogenesis.•SASPs induce collagen synthesis, one of the hallmarks of UFs.•SASPs suppress the tumor immune microenvironment which increases tumor growth.