Spatial Architecture of Myeloid and T Cells Orchestrates Immune Evasion and Clinical Outcome in Lung Cancer.
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Date
2024-06-03ICR Author
Author
Enfield, KSS
Colliver, E
Lee, C
Magness, A
Moore, DA
Sivakumar, M
Grigoriadis, K
Pich, O
Karasaki, T
Hobson, PS
Levi, D
Veeriah, S
Puttick, C
Nye, EL
Green, M
Dijkstra, KK
Shimato, M
Akarca, AU
Marafioti, T
Salgado, R
Hackshaw, A
TRACERx consortium,
Jamal-Hanjani, M
van Maldegem, F
McGranahan, N
Glass, B
Pulaski, H
Walk, E
Reading, JL
Quezada, SA
Hiley, CT
Downward, J
Sahai, E
Swanton, C
Angelova, M
Type
Journal Article
Metadata
Show full item recordAbstract
UNLABELLED: Understanding the role of the tumor microenvironment (TME) in lung cancer is critical to improving patient outcomes. We identified four histology-independent archetype TMEs in treatment-naïve early-stage lung cancer using imaging mass cytometry in the TRACERx study (n = 81 patients/198 samples/2.3 million 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, characterized by sparse lymphocytes and high tumor-associated neutrophil (TAN) infiltration, had tumor cells spatially separated from vasculature and exhibited low spatial intratumor heterogeneity. TAN-high LUSC had frequent PIK3CA mutations. TAN-high tumors harbored 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. SIGNIFICANCE: This study provides novel insights into the spatial organization of the lung cancer TME in the context of tumor immunogenicity, tumor heterogeneity, and cancer evolution. Pairing the tumor evolutionary history with the spatially resolved TME suggests mechanistic hypotheses for tumor progression and metastasis with implications for patient outcome and treatment. This article is featured in Selected Articles from This Issue, p. 897.
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Subject
Humans
Lung Neoplasms
Tumor Microenvironment
T-Lymphocytes
Myeloid Cells
Female
Male
Immune Evasion
Research team
Lung Cancer Group
Language
eng
Date accepted
2024-03-22
License start date
2024-06-03
Citation
Cancer Discovery, 2024, 14 (6), pp. 1018 - 1047
Publisher
AMER ASSOC CANCER RESEARCH