Immune cell trafficking across the blood–brain barrier and the role of the tumour immune microenvironment in cancer

The blood–brain barrier (BBB) is a specialized vascular interface that strictly regulates the exchange of cells and molecules between the bloodstream and the central nervous system, maintaining neural homeostasis and restricting immune cell entry. In primary and metastatic brain cancers, however, tumour‑driven signalling and vascular remodelling can compromise the integrity of the BBB, altering its permeability and enabling a selective influx of immune cells. Simultaneously, the tumour immune microenvironment (TIME)—comprising immune, stromal and endothelial cells together with cytokines and extracellular matrix factors—critically influences tumour growth, immune evasion and therapeutic resistance. Recent studies reveal that reciprocal interactions between BBB dysfunction and the TIME reshape local immunity, yet the precise molecular checkpoints regulating this crosstalk remain poorly defined. Deeper mechanistic insights are essential to harness immune trafficking for improving immunotherapeutic efficacy in brain malignancies.This Research Topic aims to elucidate the mechanisms governing immune cell migration across the BBB and their consequences for the TIME in both primary and secondary brain tumours. Building on—but distinct from—previous collections that broadly profiled the brain tumour immune microenvironment, this Topic focuses on the BBB as an active immune‑modulating checkpoint controlling leukocyte access and therapeutic response. Key objectives include defining the molecular pathways that mediate immune–vascular interactions, understanding neurovascular remodelling during tumour progression, and identifying factors limiting the efficacy of immune checkpoint inhibition, CAR‑T therapy and vaccines in the central nervous system. The Topic also seeks to integrate recent technological advances—such as single‑cell and spatial omics, high‑resolution imaging, organoid and BBB‑on‑chip models, and computational modelling—to uncover new therapeutic strategies that can enhance immune surveillance while preserving barrier function.This Research Topic covers basic, translational and clinical studies investigating BBB–immune–tumour interactions. Its scope focuses on how the BBB’s structure, signalling and dynamic remodelling act as mechanistic links between peripheral immunity and the TIME in brain cancers. To gather further insights, we welcome contributions addressing, but not limited to, the following themes:• Molecular and cellular pathways regulating immune cell trafficking across the BBB.• BBB remodelling, neurovascular crosstalk and vascular normalization in brain tumours.• Cellular and functional heterogeneity within the tumour immune microenvironment.• Integration of neuroimmune, stromal and endothelial signalling in tumour progression.• Single‑cell and spatial multi‑omics, live imaging and artificial‑model systems (organoids, BBB‑on‑chip).• Preclinical and clinical strategies to modulate BBB permeability and tumour immunity concurrently.• Biomarkers predicting immune infiltration, therapeutic response and patient outcome.Please 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: Ajay Singh, Rashmi Rana, Euijeon Woo, Saroj Kumar Source: https://www.frontiersin.org/research-topics/83400/immune-cell-trafficking-across-the-blood-brain-barrier-and-the-role-of-the-tumour-immune-microenvironment-in-cancer