| Title: |
Spatial Architecture of Myeloid and T Cells Orchestrates Immune Evasion and Clinical Outcome in Lung Cancer |
| Authors: |
Enfield, Katey SS; Colliver, Emma; Lee, Claudia SY; Magness, Alastair; Moore, David A; Sivakumar, Monica; Grigoriadis, Kristiana; Pich, Oriol; Karasaki, Takahiro; Hobson, Philip S; Levi, Dina; Veeriah, Selvaraju; Puttick, Clare; Nye, Emma L; Green, Mary; Dijkstra, Krijn K; Shimato, Masako; Akarca, Ayse U; Marafioti, Teresa; Salgado, Roberto; Hackshaw, Allan; Consortium, TRACERx; Jamal-Hanjani, Mariam; van Maldegem, Febe; McGranahan, Nicholas; Glass, Benjamin; Pulaski, Hanna; Walk, Eric; Reading, James L; Quezada, Sergio A; Hiley, Crispin T; Downward, Julian; Sahai, Erik; Swanton, Charles; Angelova, Mihaela |
| Source: |
Cancer Discovery , 14 (1) pp. 1-30. (2024) |
| Publisher Information: |
American Association for Cancer Research (AACR) |
| Publication Year: |
2024 |
| Collection: |
University College London: UCL Discovery |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10191382/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10191382/1/cd-23-1380.pdf; https://discovery.ucl.ac.uk/id/eprint/10191382/ |
| Rights: |
open |
| Accession Number: |
edsbas.4BC3467 |
| Database: |
BASE |