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Spatial Architecture of Myeloid and T Cells Orchestrates Immune Evasion and Clinical Outcome in Lung Cancer

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. Green open access

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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.

Type: Article
Title: Spatial Architecture of Myeloid and T Cells Orchestrates Immune Evasion and Clinical Outcome in Lung Cancer
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1158/2159-8290.CD-23-1380
Publisher version: http://dx.doi.org/10.1158/2159-8290.cd-23-1380
Language: English
Additional information: © 2024 The Authors; Published by the American Association for Cancer Research. This open access article is distributed under the Creative Commons Attribution 4.0 International (CC BY 4.0) license (http://creativecommons.org/licenses/by/4.0).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > CRUK Cancer Trials Centre
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Pathology
URI: https://discovery.ucl.ac.uk/id/eprint/10191382
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