Cancer Cell Immunotherapy: Tumor–Immune Interface and Extracellular Matrix Remodeling Signaling in Cancer Immunity

Cancer immunotherapy has transformed oncology by enabling immune cells to recognize and eliminate malignant cells, but therapeutic responses remain variable across tumor types and patients. In addition to immune checkpoint signaling, tumors actively remodel the extracellular matrix (ECM), altering its composition, organization, stiffness, and mechanical properties. These changes influence immune-cell trafficking, adhesion, activation, exhaustion, and persistence by regulating biochemical and mechanotransductive signals at the tumor–immune interface. However, the mechanisms linking ECM remodeling to intracellular signaling and immune-cell fate remain incompletely understood. Recent advances in matrix biology, mechanobiology, tumor immunology, and high-resolution tissue profiling have identified important roles for integrins, focal adhesion signaling, YAP/TAZ, ion channels, cytokine networks, and ECM-remodeling enzymes. Further investigation is needed to establish how these pathways interact in space and time and how they can be therapeutically targeted.This Research Topic aims to define how ECM remodeling regulates immune responses in tumors through the integration of biochemical, structural, and mechanical signals. We welcome studies investigating how matrix stiffness, composition, architecture, and degradation influence immune-cell infiltration, activation, dysfunction, and persistence, as well as how stromal and cancer cells coordinate these processes. A further goal is to advance therapeutic strategies that enable CAR T and NK cells to penetrate, adapt to, or overcome ECM- and stroma-mediated barriers. We also seek to promote predictive and mechanistic approaches using single-cell and spatial technologies, advanced imaging, three-dimensional models, and artificial intelligence to identify actionable determinants of immunotherapy response.To gather further insights into ECM-driven regulation of cancer immunity, this Research Topic will focus on tumor–immune interactions within remodeled extracellular matrices and on therapeutic approaches targeting the ECM, mechanotransduction pathways, and tumor stroma. Contributions may address, but are not limited to, the following themes:• ECM remodeling enzymes, including matrix metalloproteinases, lysyl oxidases, and cathepsins, in immune regulation• Matrix stiffness, composition, and architecture as determinants of immune-cell infiltration and function• Integrin, focal adhesion, YAP/TAZ, Piezo, and related mechanotransduction pathways in tumor immunity• Mechanisms linking ECM-derived cues to T-cell activation, exhaustion, exclusion, and persistence• Crosstalk between cytokine, chemokine, checkpoint, and ECM signaling networks• Interactions among cancer-associated fibroblasts, stromal cells, tumor cells, and immune infiltrates• CAR T-cell and NK-cell engineering to overcome ECM- and stroma-mediated barriers• Combination strategies involving ECM-modulating agents, immune checkpoint blockade, and adoptive cell therapy• Single-cell, spatial transcriptomic, proteomic, and T-cell receptor profiling of tumor–immune–ECM niches• Advanced imaging methods for visualizing matrix remodeling and immune-cell behavior in situ• Three-dimensional models, spheroids, tumoroids, organoids, and animal models of ECM-driven immune responses• Artificial intelligence and machine learning for predicting immune infiltration, therapeutic response, or matrix-associated resistance• Targeted interventions that reprogram ECM composition, mechanics, or signaling to enhance immunotherapy efficacy Topic editors: Angel Cid Arregui, Ibrahim Ragab Eissa, Xiyi Wei, Isaac Quiros Fernandez Source: https://www.frontiersin.org/research-topics/85339/cancer-cell-immunotherapy-tumor-immune-interface-and-extracellular-matrix-remodeling-signaling-in-cancer-immunity