Remodeling the Immune Landscape: How Obesity-Induced SASPs Create a Pro-Tumorigenic Niche
TL;DR
This review delineates how obesity-related SASPs create a permissive environment for cancer initiation and progression and targets the SASPs or the metabolic drivers of senescence as a promising therapeutic strategy to mitigate the potential oncogenic consequences of obesity.
Abstract
Obesity is a potent risk factor for cancer, primarily driven by a state of chronic inflammation. A key mechanism linking adipose tissue dysfunction to tumorigenesis is the induction of cellular senescence and the related Senescence-Associated Secretory Phenotype (SASP), which is not clearly defined. In obesity, expanding adipose tissue becomes hypoxic and stressed, triggering premature senescence in adipocytes and stromal cells. These senescent cells persistently secrete a robust arsenal of SASP factors, including pro-inflammatory cytokines (e.g., IL-6, IL-1β) and chemokines (e.g., IL-8, MCP-1). This review delineates how obesity-related SASPs create a permissive environment for cancer initiation and progression. Systemically, these SASPs establish a low-grade inflammatory milieu that promotes genomic instability and epithelial cell transformation. Within the tumor microenvironment, SASP components directly stimulate cancer cell survival, proliferation, invasion, and angiogenesis, concurrently through immune modulation. Crucially, obesity-related metabolic hormones regulate this process; hyperleptinemia, hyperinsulinemia, and hyperresistinemia amplify SASPs, while hypoadiponectinemia removes a key inhibitory brake. Obesity-induced SASPs act as critical endocrine and paracrine signals that remodel tissue landscapes to be pro-tumorigenic. Targeting the SASPs or the metabolic drivers of senescence presents a promising therapeutic strategy to mitigate the potential oncogenic consequences of obesity.