Uncovering the Adaptive Tumor Immunity Interactions from a Single‐Cell Level

The cellular, dynamics, and spatial heterogeneity of tumor adaptive immunity pose great challenges to tumor-immune cell co-culture studies. Conventional large-cell-scale models often mask the intrinsic diversity of tumor and immune cells, missing the essential information for elucidating immunotherapy mechanisms, discovering rare cell subtypes, and screening cell surface receptors. A single-cell-scale interaction model has the potential to unravel the dynamic processes among specific cell subtypes, uncovering the differences in cell interaction and the resulting divergent outcomes. This paper reports the 3D printing of a single-cell leveled immuno-oncology model to investigate adaptive immune interactions among dendritic cells, T cells, and melanoma cells. The cells within this model successfully recapitulate key motility characteristics of adaptive immunity, including recognition, presentation, cytotoxicity, and immunosuppression. The dynamic results revealed a strong correlation between cell interaction and both motility and spatial distribution, specifically showing that the duration required for contact increased by 4-6 times when the distance exceeds 60 µm. Tracking and analysis of T cells further revealed the consistency between motility and biofunctions under the stimulation of different dendritic cell types, T cell subtypes, and stimulatory factors. By reproducing cell contact events under controllable variables, the current model helps to refine and validate knowledge of immune synapses and immune-tumor cell interactions.