Systems Immunoengineering in Cancer: Decoding and Reprogramming Tumor–Immune Ecosystems

Cancer immunology is advancing rapidly as researchers seek to unravel the complex, dynamic relationships between tumor cells, immune populations, and the tumor microenvironment. Historically, the field relied heavily on descriptive approaches, but recent developments in engineering, computational biology, and high-dimensional profiling are driving a new wave of systems-level inquiry. This shift has facilitated the discovery of nuanced mechanisms shaping immune responses, revealed previously hidden sources of tumor and patient heterogeneity, and highlighted the intricacies of resistance to immunotherapies. Despite these gains, challenges remain in translating basic research into durable, broadly effective therapies, especially as tumors evolve and adapt within their immunological niches.This Research Topic aims to unite interdisciplinary efforts that bridge cutting-edge technologies, mechanistic biology, and clinical translation in the study and treatment of cancer immunity. The objective is to promote research that goes beyond observation, delivering deep mechanistic insight, presenting innovative experimental models, or advancing new therapeutic strategies. By fostering a dialogue across preclinical modeling and clinical implementation, this topic seeks to illuminate the principles that will drive the next generation of immune-based cancer therapies and address persistent obstacles such as immune escape, patient variability, and resistance mechanisms. More specifically, this Research Topic focuses on systems immunoengineering approaches that actively interrogate and reprogram tumor–immune ecosystems, with emphasis on integrated single-cell, spatial, and multi-omic profiling, perturbational model systems, and translational frameworks that enable mechanism-driven therapeutic design.The scope of this Research Topic encompasses studies that actively merge systems-level approaches, engineering innovations, and translational frameworks in cancer immunology, with a focus on strategies that improve mechanistic understanding and therapeutic potential. While the focus includes both preclinical and clinical research, studies must present clear advances in conceptual, experimental, or translational methodology. We welcome articles addressing, but not limited to, the following themes:• Systems-level analysis of tumor–immune ecosystems, including spatial and temporal immune dynamics, integrated single-cell and spatial multi-omics, and vascular–immune coupling in the tumor microenvironment• Explorations of immune heterogeneity and the regulatory principles governing immune function in cancer, including genetics-informed single-cell systems biology for identifying immune-driven disease mechanisms and therapeutic targets• Epigenetic and metabolic regulation of tumor–immune cell communication within the tumor microenvironment• Engineering and reprogramming of immune responses, including synthetic biology and immune cell circuit modulation• Development of advanced in vitro, ex vivo, or computational models that recapitulate tumor–immune interactions• Discovery and targeting of novel mechanisms for immune modulation and therapeutic intervention• Innovative translational frameworks, such as biomarker-driven patient stratification and adaptive clinical methodologies Topic editors: Miao Liu, Jinzhi Duan, Danyu Chen Source: https://www.frontiersin.org/research-topics/79822/systems-immunoengineering-in-cancer-decoding-and-reprogramming-tumor-immune-ecosystems