Engineered Microbes Transforming Immune Modulation Across Cancer, Autoimmunity, and Infection

Engineered microbes are emerging as a new class of living immunotherapeutics capable of sensing, interpreting, and actively reshaping host immune systems. Unlike conventional biologics or cell therapies with fixed mechanisms of action, engineered microbial platforms operate as dynamic systems that integrate environmental, metabolic, and immunological cues, process these inputs through programmable biological circuits, and execute context-dependent immune modulation with spatial and temporal precision. This review presents an immune-first framework that conceptualizes engineered microbes as distributed immune-computational systems defined by coordinated sensing, signal processing, memory, and effector functions embedded within host immune networks. Organizing the field around immune logic rather than microbial taxonomy or disease category, we examine how engineered microbes detect tissue-specific and immune-state signals, translate these inputs through synthetic processing modules, and generate immune outputs that activate, suppress, educate, or reprogram immunity across cancer, autoimmunity, and infectious disease. We further define immune safety architecture as a core design principle governing inflammatory control, tolerance preservation, adaptive immunity, and therapeutic termination, and discuss the translational and regulatory implications of immune-state–resolved clinical evaluation. Together, this framework positions engineered microbes as programmable immune systems and establishes a unifying conceptual foundation for their development as next-generation living immunotherapies.