Systemic inflammation, microbiota, and immune regulation in brain and leptomeningeal metastases across solid tumors

Systemic inflammation, microbiota, and immune regulation in brain and leptomeningeal metastases across solid tumorsBrain and leptomeningeal metastases represent an expanding frontier in modern oncology, where tumor biology, immune regulation, and microbiota interactions converge within the central nervous system (CNS). Across malignant entities such as non-small cell lung cancer, breast cancer, and melanoma, CNS metastases are linked to high morbidity, limited therapeutic options, and poor neurological outcomes. The CNS operates as an immune-specialized site shaped by the blood–brain and blood–CSF barriers, which restrict immune cell trafficking while generating a microenvironment distinct from systemic disease. Within this niche, specialized interactions among astrocytes, microglia, endothelial cells, and infiltrating lymphocytes influence tumor progression and immune modulation. Although genomic profiling has identified driver mutations such as EGFR, KRAS, BRAF, and ALK that contribute to CNS tropism, emerging studies reveal that systemic inflammation and host–microbiome dynamics also play decisive roles. Microbial metabolites and microbiota-derived immunomodulators influence blood–brain barrier permeability, antigen presentation, cytokine signaling, and myeloid activation, fundamentally shaping tumor–immune surveillance within the CNS. Yet, the integration of these layers—tumor genetics, microbial ecology, and immune function—remains underexplored, limiting the development of more precise therapeutic strategies.This Research Topic aims to define the convergent molecular, immunological, and microbiological mechanisms underlying brain and leptomeningeal metastases across diverse solid tumors. It seeks to elucidate how systemic inflammation, tumor-encoded genetic programs, and microbiota-derived factors interact to remodel the CNS microenvironment and govern metastatic colonization. The primary objectives are to map signaling axes connecting microbial or systemic metabolites with intracranial immune regulation, to clarify the contribution of tumor mutation spectra to microbiota–immune responses, and to identify molecular and cellular pathways that predict treatment outcomes. Additionally, this Research Topic will explore how microbial landscapes influence responses to targeted therapies or immune checkpoint inhibitors, offering insight into the role of host–microbiota–immune crosstalk in therapy resistance. By situating the microbiome within the broader context of tumor immunology and neuro-oncology, it strives to discover biomarkers and mechanistic targets that could inform future immunomicrobiota-guided interventions for CNS metastases.This Research Topic focuses on brain and leptomeningeal metastases arising from multiple solid tumor origins and welcomes both preclinical and clinical investigations. The boundaries encompass tumor genomics, immunology, and microbiome science as they pertain to CNS colonization, immune evasion, and therapy response. Contributions integrating neuroimmunology, microbial immunomodulation, and systemic inflammation are encouraged.To gather further insights into this multidisciplinary area, we welcome articles addressing, but not limited to, the following themes:- Molecular and genetic mechanisms driving brain and leptomeningeal metastases, including associations with oncogenic driver mutations.- Microbiota-derived factors and microbial metabolites influencing intracranial immune surveillance and barrier function.- Gut–brain and systemic inflammatory communication shaping metastatic colonization and immune modulation.- Cross-talk between astrocytes, microglia, and lymphocytes that defines the CNS tumor microenvironment.- Impact of microbial interventions (antibiotics, probiotics, or targeted modulation) on therapeutic response and blood–brain barrier integrity.- Multi-omics and computational profiling to link tumor mutation spectra with immune and microbial states.- Development of experimental models, including co-culture, organoid, and in vivo systems that simulate microbiome–tumor–immune interactions in the CNS.- Identification of biomarkers integrating tumor genetics, inflammation, and microbiota to guide precision immunotherapy strategies. Topic editors: Jiefei Han, Zhuoran Yao, Pankaj Kumar Panda Source: https://www.frontiersin.org/research-topics/82380/systemic-inflammation-microbiota-and-immune-regulation-in-brain-and-leptomeningeal-metastases-across-solid-tumors