作者
Katey S.S. Enfield,Emma Colliver,Claudia Lee,Alastair Magness,David A. Moore,Monica Sivakumar,Kristiana Grigoriadis,Oriol Pich,Takahiro Karasaki,Philip Hobson,Dina Levi,Selvaraju Veeriah,Clare Puttick,Emma Nye,Mary Green,Krijn K. Dijkstra,Masako Shimato,Ayse U. Akarca,Teresa Marafioti,Roberto Salgado,Allan Hackshaw,TRACERx Consortium,Mariam Jamal‐Hanjani,Febe van Maldegem,Nicholas McGranahan,Benjamin Glass,Hanna Pulaski,Eric Walk,James L. Reading,Sergio A. Quezada,Crispin T. Hiley,Julian Downward,Erik Sahai,Charles Swanton,Mihaela Angelova
摘要
Abstract Understanding the role of the tumour microenvironment (TME) in lung cancer is critical to improving patient outcome. We identified four histology-independent archetype TMEs in treatment-naive early-stage lung cancer using imaging mass cytometry in the TRACERx study (n=81 patients/198 samples/2.3million cells). In immune-hot adenocarcinomas, spatial niches of T cells and macrophages increased with clonal neoantigen burden, whereas such an increase was observed for niches of plasma and B cells in immune-excluded squamous cell carcinomas (LUSC). Immune-low TMEs were associated with fibroblast barriers to immune infiltration. The fourth archetype, characterised by sparse lymphocytes and high tumour-associated neutrophil (TAN) infiltration, had tumour cells spatially separated from vasculature and exhibited low spatial intratumour heterogeneity. TAN-High LUSC had frequent PIK3CA mutations. TAN-High tumours harboured recently expanded and metastasis-seeding subclones and had a shorter disease-free survival independent of stage. These findings delineate genomic, immune and physical barriers to immune surveillance and implicate neutrophil-rich TMEs in metastasis.