Immune cell imaging in the glioma microenvironment

Abstract

Glioblastoma remains a highly aggressive brain tumour with poor prognosis despite advances in standard therapies. The tumour microenvironment, comprising tumour cells, immune cells - predominantly tumour-associated microglia and macrophages (TAMMs) and extracellular matrix components, critically influences tumour progression and therapy resistance. TAMMs promote immunosuppression, tumour invasion, and angiogenesis, while T cells, although fewer, are suppressed by glioblastoma-mediated mechanisms, limiting anti-tumour immunity. Advances in non-invasive imaging technologies, including magnetic resonance imaging, positron emission transmission (PET), and optical methods, enable visualisation and characterisation of the immune microenvironment in vivo. Imaging agents targeting TAMM markers such as TSPO, CD163, CD68, CD206, and CX3CR1 have facilitated the mapping of immune cell distribution and functional states within gliomas. Additionally, emerging PET tracers allow monitoring of T-cell infiltration, activation, and exhaustion, providing insights into immunotherapy responses. Despite challenges such as blood brain barrier permeability, tracer specificity, and regulatory hurdles, multimodal imaging combined with radiomics and spatial transcriptomics offers promising avenues for personalised therapeutic strategies. Future directions focus on integrating immune cell imaging with theranostic approaches, nanoparticle delivery systems, and longitudinal monitoring to overcome tumour heterogeneity and improve treatment efficacy. This review highlights the evolving landscape of immune cell imaging in gliomas, emphasising its potential to enhance diagnosis, guide immunotherapy, and ultimately improve patient outcomes.