Collagen heterogeneity: a barrier and bridge driving tumor immune microenvironment remodeling

The tumor microenvironment (TME) is a complex system composed of the extracellular matrix (ECM) and various cell types, with collagen being one of its core components. Collagen heterogeneity profoundly influences tumor progression and the remodeling of the immune microenvironment by regulating tumor cell behavior, signaling pathways, and immune evasion in TME. Different subtypes of collagen significantly affect tumor growth, metastasis, and therapeutic responses by modulating the infiltration and function of immune cells. In "cold" tumors, the immunosuppressive microenvironment is shaped by collagen deposition, fibroblast activation, and the release of immunosuppressive factors. The excessive accumulation of collagen hinders immune cell infiltration and the efficacy of immunotherapy. Now, therapeutic strategies targeting collagen metabolism have shown promise in converting cold tumors into "hot" tumors by reducing collagen deposition and enhancing tumor immunity. This review systematically explores how different collagen subtypes regulate collagen metabolism offering new perspectives for the treatment of cold tumors and laying the theoretical groundwork for future advances in personalized immunotherapy.