Enfield, Katey SS;
Colliver, Emma;
Lee, Claudia SY;
Magness, Alastair;
Moore, David A;
Sivakumar, Monica;
Grigoriadis, Kristiana;
... Angelova, Mihaela; + view all
(2024)
Spatial Architecture of Myeloid and T Cells Orchestrates Immune Evasion and Clinical Outcome in Lung Cancer.
Cancer Discovery
, 14
(1)
pp. 1-30.
10.1158/2159-8290.CD-23-1380.
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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.
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