Spatial immunophenotyping of the tumour microenvironment in non-small cell lung cancer.

Autor: Backman M; 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., Lindberg A; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden., Mattsson JSM; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden., Elfving H; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden., Brunnström H; Division of Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden., O'Reilly A; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden., Bosic M; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Faculty of Medicine, University of Belgrade, Belgrade, Serbia., Gulyas M; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden., Isaksson J; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Department of Respiratory Medicine, Gävle Hospital, Gävle, Sweden., Botling J; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden., Kärre K; Department of Microbiology, Cell and Tumor Biology, Karolinska Institutet, Stockholm, Sweden., Jirström K; Division of Oncology and Therapeutic Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden., Lamberg K; Department of Respiratory Medicine, Akademiska Sjukhuset, Uppsala, Sweden., Pontén F; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden., Leandersson K; Department of Translational Medicine, Lund University, Skånes University Hospital, Malmö, Sweden., Mezheyeuski A; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Molecular Oncology Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain., Micke P; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. Electronic address: patrick.micke@igp.uu.se.
Jazyk: angličtina
Zdroj: European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2023 May; Vol. 185, pp. 40-52. Date of Electronic Publication: 2023 Feb 24.
DOI: 10.1016/j.ejca.2023.02.012
Abstrakt: 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.
Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: K.L. is a board member of Cantargia AB, a company developing IL1RAP inhibitors. This does not alter the author's adherence to all guidelines for publication and does not present a conflict of interest. All authors otherwise declare no conflicts of interest.
(Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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