Letter to the editor (Scientific journals)
Immune evasion before tumour invasion in early lung squamous carcinogenesis
Mascaux, C.; Angelova, M.; Vasaturo, A. et al.
2019In Nature, 571 (7766), p. 570-575
 

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Keywords :
DNA repair; Letter
Abstract :
[en] Early detection and treatment are critical for improving the outcome of patients with cancer1. Understanding the largely uncharted biology of carcinogenesis requires deciphering molecular processes in premalignant lesions, and revealing the determinants of the intralesional immune reaction during cancer development. The adaptive immune response within tumours has previously been shown to be strongest at the earliest stage of carcinoma2,3. Here we show that immune activation and immune escape occur before tumour invasion, and reveal the relevant immune biomarkers of the pre-invasive stages of carcinogenesis in the lung. We used gene-expression profiling and multispectral imaging to analyse a dataset of 9 morphological stages of the development of lung squamous cell carcinoma, which includes 122 well-annotated biopsies from 77 patients. We identified evolutionary trajectories of cancer and immune pathways that comprise (1) a linear increase in proliferation and DNA repair from normal to cancerous tissue; (2) a transitory increase of metabolism and early immune sensing, through the activation of resident immune cells, in low-grade pre-invasive lesions; (3) the activation of immune responses and immune escape through immune checkpoints and suppressive interleukins from high-grade pre-invasive lesions; and, ultimately, (4) the activation of the epithelial–mesenchymal transition in the invasive stage of cancer. We propose that carcinogenesis in the lung involves a dynamic co-evolution of pre-invasive bronchial cells and the immune response. These findings highlight the need to develop immune biomarkers for early detection as well as immunotherapy-based chemopreventive approaches for individuals who are at high risk of developing lung cancer. © 2019, The Author(s), under exclusive licence to Springer Nature Limited.
Disciplines :
Oncology
Author, co-author :
Mascaux, C.;  Department of Intensive Care and Thoracic Oncology, Jules Bordet Institute, Centre des Tumeurs de l’Université Libre de Bruxelles (ULB), ULB, Brussels, Belgium, Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, United States, INSERM UMR 1068, CNRS UMR 725, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix-Marseille Université, Marseille, France, Department of Multidisciplinary Oncology and Innovative Therapeutics, Assistance Publique-Hôpitaux de Marseille (AP-HM), Marseille, France, Department of Pulmonology, Strasbourg University Hospital, Strasbourg, France, INSERM IRFAC UMR_S1113, Université de Strasbourg, Strasbourg, France
Angelova, M.;  INSERM, Laboratory of Integrative Cancer Immunology, Centre de Recherche des Cordeliers, Paris, France, Equipe Labellisée Ligue Contre le Cancer, Paris, France, Sorbonne Université, Paris, France, Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot, Université de Paris, Paris, France, Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, United Kingdom
Vasaturo, A.;  INSERM, Laboratory of Integrative Cancer Immunology, Centre de Recherche des Cordeliers, Paris, France, Equipe Labellisée Ligue Contre le Cancer, Paris, France, Sorbonne Université, Paris, France, Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot, Université de Paris, Paris, France
Beane, J.;  Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, United States
Hijazi, K.;  Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, United States
Anthoine, G.;  Department of Intensive Care and Thoracic Oncology, Jules Bordet Institute, Centre des Tumeurs de l’Université Libre de Bruxelles (ULB), ULB, Brussels, Belgium
Buttard, B.;  INSERM, Laboratory of Integrative Cancer Immunology, Centre de Recherche des Cordeliers, Paris, France, Equipe Labellisée Ligue Contre le Cancer, Paris, France, Sorbonne Université, Paris, France, Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot, Université de Paris, Paris, France
Rothe, F.;  Breast Cancer Translational Research Laboratory, Jules Bordet Institute, Centre des Tumeurs de l’Université Libre de Bruxelles (ULB), ULB, Brussels, Belgium
Willard-Gallo, K.;  Laboratory of Molecular Immunology, Jules Bordet Institute, Centre des Tumeurs de l’Université Libre de Bruxelles (ULB), ULB, Brussels, Belgium
Haller, A.;  Department of Pathology, Jules Bordet Institute, Centre des Tumeurs de l’Université Libre de Bruxelles (ULB), ULB, Brussels, Belgium, Pathology Centre, Strasbourg, France
Ninane, V.;  Department of Pulmonary Medicine, CHU Saint-Pierre, Université Libre de Bruxelles (ULB), ULB, Brussels, Belgium
Burny, Arsène ;  Université de Liège - ULiège > Agro Biotech Gembloux
Sculier, J.-P.;  Department of Intensive Care and Thoracic Oncology, Jules Bordet Institute, Centre des Tumeurs de l’Université Libre de Bruxelles (ULB), ULB, Brussels, Belgium
Spira, A.;  Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, United States
Galon, J.;  INSERM, Laboratory of Integrative Cancer Immunology, Centre de Recherche des Cordeliers, Paris, France, Equipe Labellisée Ligue Contre le Cancer, Paris, France, Sorbonne Université, Paris, France, Sorbonne Paris Cité, Université Paris Descartes, Université Paris Diderot, Université de Paris, Paris, France
More authors (5 more) Less
Language :
English
Title :
Immune evasion before tumour invasion in early lung squamous carcinogenesis
Publication date :
July 2019
Journal title :
Nature
ISSN :
0028-0836
eISSN :
1476-4687
Publisher :
Nature Publishing Group
Volume :
571
Issue :
7766
Pages :
570-575
Funders :
National Lung Cancer Partnership
CNRS - Centre National de la Recherche Scientifique [FR]
INSERM - Institut National de la Santé et de la Recherche Médicale [FR]
Ligue Contre le Cancer
ASRF - Applied Scientific Research Fund [JO]
LUNGevity Foundation [US-IL] [US-IL]
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