Engineering 3D bioprinted tumor-immune microenvironments to advance cancer immunotherapy

The field of cancer immunotherapy has witnessed remarkable progress over the past decade, offering durable benefits for subsets of patients across multiple malignancies. However, resistance and immune evasion remain formidable clinical barriers. Tumor cells can manipulate immune checkpoints, remodel stromal and vascular architectures, and generate immunosuppressive microenvironments that limit immune infiltration, promote T cell exhaustion, and blunt therapeutic efficacy. Standard two-dimensional cultures and animal models often fail to reproduce the biochemical gradients, mechanical constraints, and multicellular signaling found in human tumors. Recent initiatives by the FDA and NIH toward New Approach Methodologies (NAMs) have underscored the need for physiologically relevant, human-based models that can enhance translational predictivity while reducing dependence on animal testing. Emerging 3D bioprinting technologies—encompassing extrusion, inkjet, drop-on-demand, and light-based patterning such as digital light processing (DLP) and stereolithography—enable the precise spatial deposition of cell-laden biomaterials. These systems can recapitulate tumor architecture, extracellular matrix mechanics, and dynamic immune-tumor interactions with unprecedented control, thus providing a powerful platform to study antitumor immunity in a structured, controllable context.This Research Topic aims to elucidate how engineered three-dimensional tumor-immune microenvironments can help uncover mechanisms of immune suppression and resistance to immunotherapy in solid tumors. By integrating multicellular composition, biophysical cues, and immunological complexity, 3D bioprinted models offer unique opportunities to examine how matrix stiffness, spatial patterning, permeability, and stromal composition shape immune recognition and cytotoxic function. Contributions are encouraged that map design parameters—such as bioink formulations, crosslinking, perfusion systems, or immune cell seeding strategies—to measurable immunological outcomes including antigen presentation, T cell migration and killing, cytokine signaling, macrophage polarization, or checkpoint dynamics. The goal is to promote standardized, reproducible, NAM-aligned systems capable of bridging preclinical discovery and clinical translation. We welcome studies that use cutting-edge methodologies such as high-resolution printing, live-cell imaging, spatial transcriptomics, or multiplex immune profiling to improve our understanding of tumor-immune crosstalk and to accelerate the development of effective therapeutic combinations.To gather further insights into advances in 3D bioprinted tumor-immune modeling and its translational potential, we welcome articles addressing, but not limited to, the following themes:• Bioprinted tumor models integrating cancer, stromal, endothelial, and immune compartments using patient-derived or organoid-informed cells• Mechanistic studies of immune infiltration, exclusion, recognition, exhaustion, and stromal immunosuppression within printed microenvironments• Evaluation of immune checkpoint inhibitors, antibody therapies, adoptive cell and engineered T/NK cell strategies, and rational immunotherapy combinations• Integration of engineering variables—including printing modality, spatial fidelity, perfusion, matrix composition, vascular mimicry, oxygenation, and chemokine gradients—linked to quantifiable immune readouts• Technical and methodological innovations improving viability, reproducibility, scalability, imaging, and benchmarking toward validation of bioprinted tumor-immune platforms as NAMs for regulatory and translational applicationManuscript types of interest include Original Research, Methods, Reviews, Mini Reviews, and Perspectives.Please note: Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.Please note that Dr. Zheng Zhong is a VP of R&D at TissueGenix, Inc., and is also a technical consultant at the University of California, San Diego in the area of 3D bioprinting and disease modeling. Dr. Stephanie Michelle Willerth is the CEO of Axolotl Biosciences, holds grants from NSERC, ACET, CIHR, MITACS, CFI, and BCKDF, and holds a patent in the area of bioprinting. Topic editors: ZHENG ZHONG, Stephanie Michelle Willerth Source: https://www.frontiersin.org/research-topics/81619/engineering-3d-bioprinted-tumor-immune-microenvironments-to-advance-cancer-immunotherapy