Matter of Fat: Cancer‐Associated Adipocytes as Mediators of Tumor Progression and Immune Evasion

ABSTRACT Peritumoral adipocytes that exhibit changes in their phenotype and distinct biological characteristics, such as reduced expression of mature adipocyte differentiation markers, increased secretion of adipocyte‐derived factors, and facilitation of metabolic reprogramming in cancer cells, are referred to as cancer‐associated adipocytes (CAAs). CAAs are increasingly recognized as important contributors to tumor initiation, progression, and metastasis within the tumor microenvironment (TME). Found predominantly in fat‐rich tissues such as breast, ovarian, colorectal, and pancreatic cancers, CAAs undergo significant functional changes when exposed to cancer cells. These changes include lipid transfer to cancer cells, secretion of pro‐inflammatory cytokines, and remodeling of the extracellular matrix, all of which enhance cancer cell survival, proliferation, and invasion. The TME, composed of various non‐cancerous cells, extracellular matrix components, and signaling molecules, plays a dynamic role in influencing tumor behavior and treatment response. CAAs engage in a reciprocal interaction with cancer cells, transforming from normal adipocytes to tumor‐promoting cells while simultaneously driving cancer aggressiveness. Understanding the mechanisms through which CAAs contribute to cancer progression offers promising avenues for novel therapeutic strategies targeting the TME to combat cancer more effectively.