Modeling Cancer with Bacteria-Integrated Tumor Microenvironments Using Biomaterials: Emerging Concepts and Opportunities

The tumor microenvironment (TME) is a dynamic and heterogeneous ecosystem in which cancer, stromal, immune, and physicochemical components collectively regulate disease progression and therapeutic response. Recent evidence further indicates that intratumoral bacteria are active contributors to tumor metabolism, immune modulation, and treatment outcomes, revealing a previously underexplored multi-kingdom dimension of solid tumors. However, mechanistic understanding of tumor–microbe interactions remain limited by the absence of experimental platforms that integrate microbial components into physiologically relevant and controllable tumor models. Here, we propose bacteria-integrated tumor microenvironments as an emerging bioengineering framework for modeling cancer as a multi-kingdom system with biomaterials. We first lay out the existence of bacteria in our body and outline key design principles for these systems, including control of microbial localization, nutrient and oxygen gradients, and interkingdom signaling within engineered matrices. We further discuss applications in studying microbial contributions to therapeutic resistance, evaluating engineered bacterial therapies, and developing patient-specific tumor–microbiome models for precision oncology. Finally, we highlight challenges in standardizing multi-kingdom tumor platforms and integrating them with advanced imaging, sequencing, and computational tools. Collectively, bacteria-integrated tumor microenvironments establish a new paradigm for engineering cancer as a multi-kingdom system with translational potential in oncology.