Immune regulatory networks driving metastasis in gastrointestinal malignancies

Gastrointestinal (GI) malignancies—including esophageal, gastric, colorectal, hepatic, and pancreatic cancers—constitute a major global health burden and rank among the top causes of cancer-related death. Metastatic spread remains the principal cause of treatment failure and mortality in these malignancies. The immune system exerts paradoxical influences throughout cancer progression: while immune surveillance can restrain tumor growth, immune evasion and remodeling of the tumor microenvironment (TME) actively promote metastatic dissemination. Accumulating evidence indicates that immune cell infiltration, cytokine networks, extracellular matrix remodeling, and immune checkpoint modulation collectively guide key events in the metastatic cascade, from epithelial-mesenchymal transition (EMT) and intravasation to colonization at distant organs. However, defining the precise immune mechanisms orchestrating each stage of metastasis remains an unmet challenge. Recent advances in multi-omics and spatial profiling now offer unprecedented opportunities to elucidate these complex regulatory interactions. This Research Topic aims to elucidate the immune regulatory circuits that govern gastrointestinal cancer metastasis at both the primary and metastatic sites. Specifically, it will explore how immune-mediated signaling promotes EMT, invasion, circulation, and the formation of pre-metastatic niches in secondary organs such as the liver, lung, and peritoneum. By integrating insights from single-cell sequencing, spatial transcriptomics, and advanced immune profiling, this Topic seeks to identify the cellular and molecular immune mediators driving metastatic progression. Ultimately, the goal is to uncover actionable immune targets and predictive biomarkers that can inform novel immunotherapeutic strategies to intercept metastatic dissemination and improve outcomes in patients with advanced GI malignancies. This Research Topic encompasses studies exploring immune regulation underlying metastatic progression in gastrointestinal cancers, from initiation to colonization. It encourages multidisciplinary approaches linking tumor immunology, molecular oncology, and translational research. Contributors are invited to submit original research, reviews, mini-reviews, perspectives, and hypothesis articles addressing, but not limited to, the following themes:• Immune cell subsets (e.g., T cells, macrophages, neutrophils, dendritic cells, innate lymphoid cells) orchestrating EMT, invasion, and intravasation• Cytokine, chemokine, and extracellular vesicle signaling mediating immune crosstalk in metastatic initiation• Mechanistic insights into pre-metastatic niche formation and remodeling in distant organs• Mechanisms of immune suppression and immune evasion facilitating metastatic colonization• Therapeutic targeting of metastatic immune microenvironments and predictive biomarkers for treatment responsePlease note: Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic. Topic editors: Yexuan Deng, Guangyan Zhangyuan, Xiang Zhong Source: https://www.frontiersin.org/research-topics/82136/immune-regulatory-networks-driving-metastasis-in-gastrointestinal-malignancies