This article describes research using multimodal spatial-omics to investigate the progression of lung precursor lesions to lung adenocarcinoma (LUAD). The authors reveal that KRT8-high alveolar intermediate cells (KACs), or reactive pneumocytes (RPII), are early precursors in LUAD development, often residing in epithelial-proinflammatory niches enriched with IL-1β–IL1R1 signaling. Through spatial transcriptomics and single-cell analysis of human and mouse samples, the study demonstrates that these proinflammatory niches are stage-specific and more prevalent in premalignant phases. Crucially, functional validation in mouse models suggests that targeting IL-1β signaling, especially in combination with PD-1 checkpoint blockade during precancerous stages, significantly reduces KAC abundance and LUAD pathogenesis.

References:

• Peng F, Sinjab A, Dai Y, et al. Multimodal spatial-omics reveal co-evolution of alveolar progenitors and proinflammatory niches in progression of lung precursor lesions[J]. Cancer Cell, 2025.