The extracellular matrix (ECM) plays a crucial role in tumor immunity by providing mechanical support, influencing the microenvironment, and serving as a reservoir for signaling molecules. The stiffness of the ECM, determined by the abundance and cross-linking of its components, is a critical factor in disrupting normal mechanotransduction and promoting malignant progression. This review comprehensively examines the following aspects: 1. **Principal Components of ECM and Their Roles**: Collagens, proteoglycans (PGs), and matricellular proteins are key components of the ECM. They influence tissue development, homeostasis, and disease processes through structural support and control of cellular activities. 2. **Interactions Between ECM and Immune Cells**: The ECM interacts with immune cells in the tumor microenvironment (TME) through various mechanisms, including the secretion of signals that govern immune cell functions. These interactions are essential for understanding the dynamics of immune cell behavior in the TME. 3. **Pivotal Regulators of Onco-immune Response**: Key regulators such as integrins, discoidin domain receptors (DDR), and hyaluronan receptor CD44 transduce matrix signals, regulating multiple cellular functions including adhesion, cytoskeletal dynamics, cell proliferation, survival, and differentiation. The review highlights how the ECM's stiffness and composition can impede immune cell migration, alter immune cell phenotypes, and influence immune responses. For example, tumor-associated macrophages (TAMs) degrade and synthesize ECM components, forming a reactive stroma that supports tumor growth. Neutrophils and dendritic cells also play significant roles in ECM remodeling, influencing immune cell migration and activation. The stiffness of the ECM can affect T cell dynamics, leading to reduced cytotoxic activity and increased regulatory T cell markers. Additionally, the ECM's mechanical properties can modulate the behavior of antigen-presenting cells (APCs) such as macrophages and dendritic cells, affecting immune responses in the TME. Overall, the review underscores the complex interplay between the ECM and immune cells in tumor immunity, providing insights into potential therapeutic targets for cancer treatment.The extracellular matrix (ECM) plays a crucial role in tumor immunity by providing mechanical support, influencing the microenvironment, and serving as a reservoir for signaling molecules. The stiffness of the ECM, determined by the abundance and cross-linking of its components, is a critical factor in disrupting normal mechanotransduction and promoting malignant progression. This review comprehensively examines the following aspects: 1. **Principal Components of ECM and Their Roles**: Collagens, proteoglycans (PGs), and matricellular proteins are key components of the ECM. They influence tissue development, homeostasis, and disease processes through structural support and control of cellular activities. 2. **Interactions Between ECM and Immune Cells**: The ECM interacts with immune cells in the tumor microenvironment (TME) through various mechanisms, including the secretion of signals that govern immune cell functions. These interactions are essential for understanding the dynamics of immune cell behavior in the TME. 3. **Pivotal Regulators of Onco-immune Response**: Key regulators such as integrins, discoidin domain receptors (DDR), and hyaluronan receptor CD44 transduce matrix signals, regulating multiple cellular functions including adhesion, cytoskeletal dynamics, cell proliferation, survival, and differentiation. The review highlights how the ECM's stiffness and composition can impede immune cell migration, alter immune cell phenotypes, and influence immune responses. For example, tumor-associated macrophages (TAMs) degrade and synthesize ECM components, forming a reactive stroma that supports tumor growth. Neutrophils and dendritic cells also play significant roles in ECM remodeling, influencing immune cell migration and activation. The stiffness of the ECM can affect T cell dynamics, leading to reduced cytotoxic activity and increased regulatory T cell markers. Additionally, the ECM's mechanical properties can modulate the behavior of antigen-presenting cells (APCs) such as macrophages and dendritic cells, affecting immune responses in the TME. Overall, the review underscores the complex interplay between the ECM and immune cells in tumor immunity, providing insights into potential therapeutic targets for cancer treatment.