The lung tumour microenvironment is a complex and evolving ecosystem in which immune, stromal and malignant cells interact across both space and time. Spatial organisation determines whether immune cells can access and induce immune responses across tumour tissues, while temporal changes driven by disease progression and therapy reshape these interactions. Although advances in high-plex technologies have revealed discrete immune niches in lung cancer, particularly in nonsmall cell lung carcinoma (NSCLC), less is known about how these tissue landscape niches remodel over time. This review integrates spatial and temporal perspectives to provide a unified view of lung cancer immunobiology. We discuss how fibroblast activation, endothelial remodelling and extracellular matrix deposition restrict immune infiltration and how conventional therapies and targeted inhibitors can remodel these barriers. We highlight recent studies that reveal how immune functional states shift with treatment and cancer stages. Finally, we outline how emerging technologies (spatial transcriptomics, multiplex imaging and functional assays) offer new opportunities to link temporal transitions with spatial immune context. Understanding spatiotemporal dynamics will be key to stage-specific biomarker discovery, treatment optimisation and personalised strategies in NSCLC.
Wong et al. (2026) studied this question.