Inflammation and immune suppression drive breast cancer in aging women

Inflammation and immune suppression drive breast cancer in aging women

Age-related and postmenopausal progression of breast cancer remains a significant challenge, with growing evidence pointing to the role of proinflammatory cytokines and CXC chemokines in the development of tumor and immune systems. As the world's population ages, understanding the intricate links between aging, inflammation and cancer progression becomes increasingly critical.

The aging process is accompanied by changes in the tumor microenvironment, including the stiffening of the extracellular matrix and the accumulation of inflammatory immune mediators, such as interleukins (IL-6, IL-8), tumor necrosis factor (TNF), transforming growth factor (TGF), and CXC chemokines (CXCL1, CXCL9, CXCL10, CXCL11, CXCL12). These factors contribute to tumor growth, metastasis, and immune signaling, particularly in postmenopausal women.

Obesity-induced chronic inflammation further increases the risks as excess adipose tissue leads to overproduction of cytokines and adipokines. This inflammatory environment enhances tumor aggressiveness, influences immune cell infiltration, and alters hormone signaling, thereby increasing breast cancer susceptibility in postmenopausal women. Studies have shown that increased levels of CXCL8/IL-8 and CXCL12/CXCR4 correlate with tumor progression, making these important targets for potential therapeutic interventions.

A crucial aspect of progressive breast cancer is immune dysregulation, particularly the decline in tumor-infiltrating lymphocytes (TILs) and impaired response to immune checkpoint inhibitors. The senescence-associated secretory phenotype (SASP), characterized by the release of inflammatory cytokines, plays a central role in this process, contributing to both tumor growth and immune suppression. The pro-tumor effects of IL-6, IL-1β and CXCLs highlight the importance of cytokine-driven inflammation as a therapeutic strategy.

Advances in theranostic interventions focused on cytokine and chemokine modulation hold promise for improved treatment of breast cancer in older women. By addressing the interplay between aging, obesity, inflammation and immune function, researchers aim to develop personalized therapies that mitigate tumor progression while preserving immune surveillance.

With the increasing incidence of postmenopausal breast cancer, the need for innovative approaches targeting inflammatory pathways has never been more urgent. By deciphering the complex molecular mechanisms underlying cancer progression, the scientific community is paving the way for more effective and tailored treatment strategies that can significantly improve patient outcomes.

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