Immune evasion before tumour invasion in early lung squamous carcinogenesis

[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

More authors (5 more)

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

Additional URL :

https://www.nature.com/articles/s41586-019-1330-0

Funders :

National Lung Cancer Partnership
CNRS - Centre National de la Recherche Scientifique
INSERM - Institut National de la Santé et de la Recherche Médicale
Ligue Contre le Cancer
ASRF - Applied Scientific Research Fund
LUNGevity Foundation

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since 25 October 2019

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