Perivascular spaces are associated with T cell trafficking and may have prognostic relevance in brain metastases

Abstract Background Perivascular structures, in particular, perivascular spaces (PVS) are emerging key immune modulators in the tumor microenvironment. However, their relationship with immune infiltration, vascular remodeling, and clinical outcomes in brain metastases is unclear. Methods In this retrospective two-center study, we analyzed 56 brain metastases. Perivascular spaces were graded on preoperatively T2-weighted MRI in the basal ganglia and centrum semiovale. Tumor immune infiltration, vascular features, and immune cell phenotypes were assessed by immunohistochemistry and spectral flow cytometry and correlated with clinical outcome. Results Here we show that high PVS burden in the centrum semiovale region, but not in the basal ganglia, were significantly associated with improved overall survival. High PVS are linked to increased presence of tumor-infiltrating cytotoxic T cells—most of which exhibited an activated/exhausted phenotype, indicated by PD-1- and Fas-positivity—was likewise prognostically favorable. Moreover, these cells showed elevated expression of the migration marker CXCR3, as well as Granzyme B/IFNγ consistent with effector polarization. High PVS were additionally associated with a higher M1/M2-like macrophage ratio, which showed similar prognostic relevance as high vascular density, suggesting enhanced blood supply and immune cell recruitment. Conclusion These findings could establish PVS as a non-invasive imaging marker of anti-tumor immunity and prognosis in patients with brain metastasis, underscoring their potential as biomarkers for immune activity and therapeutic monitoring.