Periostin within the tumor microenvironment: molecular insights and immunomodulatory roles in cancer

Periostin, also known as osteoblast-specific factor 2 (OSF-2), is a secreted matricellular protein with pleiotropic functions in both physiological and pathological processes. While it contributes to tissue repair, bone remodeling, and cardiovascular and respiratory homeostasis, accumulating evidence highlights its critical role in cancer progression. In diverse malignancies—including esophageal, gastric, colorectal, pancreatic, hepatocellular, ovarian, lung, breast carcinomas, and glioma—periostin is frequently overexpressed in both the stromal and epithelial compartments. Its regulation is consistently correlated with increased tumor invasiveness, advanced clinical stage, poor prognosis, and shortened patient survival. Mechanistically, periostin promotes tumor progression through multiple interconnected pathways, including the activation of NF-κB and AKT signaling, induction of epithelial–mesenchymal transition, stimulation of angiogenesis, and maintenance of cancer stemness. Within the tumor microenvironment, periostin-expressing cancer-associated fibroblasts drive extracellular matrix remodeling, establish an immunosuppressive niche, and impede CD8 + T-cell infiltration, thereby attenuating antitumor immunity and limiting responses to immunotherapy. This review systematically summarizes the structure, expression, and multifaceted functions of periostin, with a particular focus on its immunomodulatory actions within the tumor microenvironment, and discusses its emerging potential as a prognostic biomarker and therapeutic target in cancer immunotherapy.