Armored and Cold Tumors: A Refractory Subset of Solid Cancer

Solid tumors are characterized by extensive extracellular matrix (ECM) remodeling prominently featuring massive collagen deposition. This dense collagen network does not act as inert scaffolding but actively orchestrates critical aspects of tumor progression and therapy resistance, thereby shaping the fate of cancer cells. Collagen influences cellular behavior through multiple mechanisms, including providing structural rigidity, modulating mechanotransduction signaling pathways, creating physical barriers to immune cell infiltration and drug penetration, and serving as a reservoir for signaling molecules. Here, we discuss recent findings regarding the critical roles of collagen in tumors and potential therapies for armored and cold tumors, a refractory subset demonstrating high collagen deposition and low immune infiltration.