The crosstalk between cancer cells and the immune system within the tumor microenvironment (TME) governs the efficacy of immunotherapeutic interventions. However, conventional preclinical models fail to recapitulate these dynamic processes.
Microphysiological systems, particularly immunocompetent tumor-on-a-chip (TOC) platforms, bridge the gap between simplified two-dimensional cultures and animal models. These devices integrate microfluidic engineering, biomimetic extracellular matrices, and controlled perfusion.
These platforms effectively recapitulate the cellular heterogeneity, three-dimensional structure, and physiological flow conditions of the TME. This review examines the engineering principles of immunocompetent TOC platforms and their applications in cancer immunotherapy research.
These systems enable mechanistic studies of the cancer-immunity cycle, including immune cell recruitment, migration, and tumor cell cytotoxicity. They are particularly valuable for evaluating cell-based immunotherapies, including CAR-T cells.
TOC platforms also facilitate drug screening and the testing of combination therapies. They show promise for functional precision oncology when integrated with patient-derived cells.
Recent advances have extended these models toward greater physiological complexity. For example, multi-organ-on-a-chip systems capture systemic interactions, while lymph node-on-a-chip platforms enable studies of immune activation, and additionally organ-specific models mimic metastatic sites.
Frontiers in Immunology published a clinical update in Infectious Disease on 14 May 2026.
The item focuses on Microfluidic chips for decoding cancer-immune crosstalk in immunotherapy.
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