Abstract

Pericytes display marked tissue-specific transcriptional identities, raising the question of whether tumour-associated pericytes converge towards shared adaptive states across cancers. Here, we built a pan-cancer single-cell RNA sequencing atlas of pericytes, integrating nearly four million cells across nine tissues, complemented by spatial transcriptomic analyses. Despite their physiological diversity, pericytes were recurrently expanded in tumours and converged on a common transcriptional program, the tumour-associated pericyte signature (TAPS). TAPS robustly identified pericytes across datasets, outperforming canonical markers in tumour contexts. Tumour-associated pericytes further diversified into specialised states including extracellular matrix (ECM)-associated and interferon (IFN)-responsive programs, which occupy mutually exclusive tumour ecosystems. ECM-associated pericytes were enriched in desmoplastic, fibroblast-rich regions and were associated with adverse clinical outcomes across multiple cancer types. IFN-responsive pericytes accumulated in inflammatory niches, with macrophages implicated as candidate drivers of specialisation. Together, our multi-layered analysis defines convergent and specialised tumour-associated pericyte programs across human cancers.