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Issue 378: We developed MISSTE, a multiscale integrative spatial simulator to model tissue ecosystems. The colored heat map in the figure represents dynamic microenvironmental fields during simulations, while the scattered cells show agent-based cell movement and interactions. The network inside the tissue-like boundary suggests intracellular decision logic, where cells respond to signals such as oxygen, cytokines, suppression, and contact with other cells. We applied MISSTE to explain complex behavior of CAR-T therapy for solid tumors, including limited tumor penetration, stromal suppression, hypoxia, cytokine remodeling, and T-cell exhaustion.