The challenge is that the tumor immune microenvironment is not a static backdrop but a constantly shifting ecosystem shaped by cancer cells, immune cells, stromal cells, cytokines, and physical barriers. Traditional animal models remain informative but are expensive, slow, ethically constrained, and imperfect mirrors of human disease. Standard 2D systems such as Transwell assays are simpler and reproducible, yet they cannot fully reproduce fluid dynamics, spatial organization, or the real-time immune pursuit of tumor cells. Microfluidic systems have attracted growing attention because they can better mimic these spatiotemporal interactions, provide three-dimensional architectures, and support more realistic drug testing. Based on these challenges, deeper research is needed into microfluidic strategies for decoding tumor–immune crosstalk and improving immunotherapy.
Researchers from the Medical Research Center at Southern University of Science and Technology Hospital and the School of Medicine at Southern University of Science and Technology reported (DOI: 10.20892/j.issn.2095-3941.2025.0541)in Cancer Biology & Medicine, that microfluidic platforms are emerging as versatile tools for modeling tumor–immune interactions, evaluating immunotherapy efficacy, and preparing immunotherapeutic agents for more personalized cancer treatment.
What makes the review especially compelling is its range. The authors describe chip-based models that track macrophage migration toward tumor cells under chemokine gradients, show how stromal barriers can block immune infiltration, and recreate vascular steps such as cancer-cell intravasation and extravasation. Other systems capture single-cell heterogeneity, including the striking finding from cited work that not all natural killer cells kill equally, making microfluidics valuable for exposing hidden functional differences. The review also highlights platforms for testing cellular therapies such as TCR-T, CAR-T, and NK-cell approaches, as well as immune checkpoint blockade in patient-derived tissues, organoids, and tumor fragments. Beyond modeling, microfluidics can manufacture therapeutic components, including NK-cell-containing porous microspheres, nanoparticles, and engineered exosomes designed to improve antigen presentation and immune activation. Together, these applications point to a technology that is not only observing tumor immunity, but actively shaping the future toolkit of cancer therapy.
"Microfluidic chips have been considered potential preclinical models for testing and predicting the efficacy of immunotherapies," the authors conclude, while also emphasizing that no single in vitro or ex vivo platform can yet replicate the full complexity of the living tumor microenvironment. They argue that the field's next steps should include better validation against in vivo tumors, closer correlation with clinical specimens, longer ex vivo culture times, and more practical medium- to high-throughput systems for translational use.
The implications are broad. In the near term, microfluidic systems could help researchers screen drug combinations faster, identify biomarkers more accurately, and compare which patients are most likely to respond to immunotherapy. Over time, these chips may support a more personalized oncology workflow in which a patient's own tumor tissue and immune cells are tested on-chip before treatment decisions are made. The review also suggests that pairing microfluidics with 3D printing, thermoplastic manufacturing, and artificial intelligence could accelerate commercialization and data interpretation. If those advances continue, tiny chips may become powerful engines for smarter, more individualized cancer care.
###
References
DOI
10.20892/j.issn.2095-3941.2025.0541
Original Source URL
https://doi.org/10.20892/j.issn.2095-3941.2025.0541
Funding information
This work was supported by grants from the National Natural Science Foundation of China (Grant No. 82371747), the Guangdong Basic and Applied Basic Research Foundation (Grant Nos. 2021A1515010115 and 2022A1515012625), the Shenzhen Science and Technology Program (Grant Nos. JCYJ20210324103611030 and JCYJ20240813093903005), the Nanshan District Health System Technology Major Project (Grant Nos. NSZD2023056 and NSZD2024070), and the Southern University of Science and Technology Hospital Foundation for High-level Talents (Grant No. 2021-012).
About Cancer Biology & Medicine
Cancer Biology & Medicine (CBM) is a peer-reviewed open-access journal sponsored by China Anti-cancer Association (CACA) and Tianjin Medical University Cancer Institute & Hospital. The journal monthly provides innovative and significant information on biological basis of cancer, cancer microenvironment, translational cancer research, and all aspects of clinical cancer research. The journal also publishes significant perspectives on indigenous cancer types in China. The journal is indexed in SCOPUS, MEDLINE and SCI (IF 8.4, 5-year IF 6.7), with all full texts freely visible to clinicians and researchers all over the world.