Organ-specific metastasis and the immune landscape: Mechanisms and therapeutic opportunities

Metastasis remains the leading cause of cancer-related mortality, with distinct organs such as lung, liver, bone, and brain exhibiting preferential colonization by primary tumors. This organotropism is not merely passive but is actively shaped by the interplay between tumor cells and the local immune microenvironment. Emerging evidence indicates that pre-metastatic niches, immune cell composition, and stromal architecture differ markedly across metastatic sites, profoundly influencing tumor outgrowth and therapeutic response. However, the immunological determinants of organ-specific metastasis remain incompletely understood. This Research Topic aims to gather current insights into how organ-resident immune landscapes govern metastatic progression and to identify targetable nodes for intervention.The central problem is that current immunotherapies yield inconsistent responses across different metastatic sites, partly due to a one-size-fits-all approach that overlooks organ-specific immune heterogeneity. To achieve more precise and effective treatments, we need a systematic understanding of how the immune landscape varies among organs and how tumor cells co-opt these differences for metastatic advantage. This Research Topic seeks to bridge this gap by collating mechanistic studies and translational perspectives on organ-specific immune–tumor interplay. By highlighting recent advances in single-cell technologies, spatial transcriptomics, and in vivo models, we aim to uncover novel biomarkers and therapeutic targets tailored to distinct metastatic niches. Ultimately, this collection aspires to inform next-generation immunotherapies that account for organ tropism, thereby improving outcomes for patients with advanced metastatic disease. This Research Topic welcomes Original Research, Reviews, Mini-Reviews, and Opinion articles addressing the immunological underpinnings of organ-specific metastasis. Specific themes of interest include, but are not limited to:• Organ-specific pre-metastatic niche formation and immune remodeling• Divergent immune cell functions (e.g., macrophages, neutrophils, NK cells) in metastatic sites such as lung, liver, brain, and bone• Crosstalk between metastatic tumor cells and organ-resident stromal or immune populations• Immunogenomic and spatial determinants of organotropic metastasis• Preclinical models and emerging technologies to study immune-metastatic interactions• Therapeutic strategies targeting organ-specific immune landscapes (e.g., immunomodulators, combination therapies).Please note that manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation (clinical cohort or biological validation in vitro or in vivo) are out of scope for this Research Topic. Manuscripts focusing solely on cost-effectiveness studies are also not considered for publication in this journal. Topic editors: Ming-Zhu Jin, Julia Schueler Source: https://www.frontiersin.org/research-topics/83507/organ-specific-metastasis-and-the-immune-landscape-mechanisms-and-therapeutic-opportunities