Hidden Architecture of Resistance: The Extracellular Matrix in Melanoma’s Immune Landscape

Tumor heterogeneity in cutaneous melanoma (CM) is attributed to the functional and structural diversity of tumor cells, immune cells, and the tumor stroma, and determines patients' response to therapy. The tumor immune microenvironment (TIME) comprises a diverse array of cellular and non-cellular components. Cells include cancer-associated fibroblasts, T cells, NK cells, B cells, dendritic cells, myeloid-derived suppressor cells, and monocytes. Non-cellular components include cytokines, growth factors, and extracellular matrix (ECM). In this review, we specifically focus on the critical roles of ECM molecules, namely collagen, fibronectin, laminin, hyaluronic acid, galectin, and matrix metalloproteinase, in shaping the melanoma TIME. We explore ECM components by examining how their physical properties and biological functions regulate the interactions between cancer and immune cells, thereby impacting immunity in melanoma and underscoring their clinical significance.