Sistema de Salut de Catalunya
Institut Català de la Salut
[Backman M, Lindberg A, Mattsson JSM, Elfving H] Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. [Strell C] Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, University of Bergen, Bergen, Norway. [Brunnström H] Division of Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden. [Mezheyeuski A] Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. Molecular Oncology Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2023-05-22T12:42:00Z
2023-05-22T12:42:00Z
2023-05
Checkpoint therapy; Lung cancer; Tumour microenvironment
Terapia de puntos de control; Cáncer de pulmón; Microambiente tumoral
Teràpia de punts de control; Càncer de pulmó; Microambient tumoral
Introduction: Immune cells in the tumour microenvironment are associated with prognosis and response to therapy. We aimed to comprehensively characterise the spatial immune phenotypes in the mutational and clinicopathological background of non-small cell lung cancer (NSCLC). Methods: We established a multiplexed fluorescence imaging pipeline to spatially quantify 13 immune cell subsets in 359 NSCLC cases: CD4 effector cells (CD4-Eff), CD4 regulatory cells (CD4-Treg), CD8 effector cells (CD8-Eff), CD8 regulatory cells (CD8-Treg), B-cells, natural killer cells, natural killer T-cells, M1 macrophages (M1), CD163+ myeloid cells (CD163), M2 macrophages (M2), immature dendritic cells (iDCs), mature dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs). Results: CD4-Eff cells, CD8-Eff cells and M1 macrophages were the most abundant immune cells invading the tumour cell compartment and indicated a patient group with a favourable prognosis in the cluster analysis. Likewise, single densities of lymphocytic subsets (CD4-Eff, CD4-Treg, CD8-Treg, B-cells and pDCs) were independently associated with longer survival. However, when these immune cells were located close to CD8-Treg cells, the favourable impact was attenuated. In the multivariable Cox regression model, including cell densities and distances, the densities of M1 and CD163 cells and distances between cells (CD8-Treg-B-cells, CD8-Eff-cancer cells and B-cells-CD4-Treg) demonstrated positive prognostic impact, whereas short M2-M1 distances were prognostically unfavourable. Conclusion: We present a unique spatial profile of the in situ immune cell landscape in NSCLC as a publicly available data set. Cell densities and cell distances contribute independently to prognostic information on clinical outcomes, suggesting that spatial information is crucial for diagnostic use.
This study was partly supported by Swedish Cancer Society, The Lions Cancer Foundation Uppsala, Sweden, Selanders Foundation and The Sjöberg Foundation, Sweden.
Article
Published version
English
Cèl·lules T; Pulmons - Càncer - Diagnòstic; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Immunologic Tests::Immunophenotyping; DISEASES::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma, Bronchogenic::Carcinoma, Non-Small-Cell Lung; Other subheadings::Other subheadings::/diagnosis; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::técnicas y procedimientos diagnósticos::técnicas de laboratorio clínico::pruebas inmunológicas::inmunofenotipificación; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma de pulmón de células no pequeñas; Otros calificadores::Otros calificadores::/diagnóstico
Elsevier
European Journal of Cancer;185
https://doi.org/10.1016/j.ejca.2023.02.012
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
