Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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

Backman, Max ; Strell, Carina ; Lindberg, Amanda ; Mattsson, Johanna S M ; Elfving, Hedvig ; Brunnström, Hans LU orcid ; O'Reilly, Aine ; Bosic, Martina ; Gulyas, Miklos and Isaksson, Johan , et al. (2023) In European Journal of Cancer 185. p.40-52
Abstract

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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Cancer
volume
185
pages
40 - 52
publisher
Elsevier
external identifiers
  • pmid:36963351
  • scopus:85150344925
ISSN
0959-8049
DOI
10.1016/j.ejca.2023.02.012
language
English
LU publication?
yes
id
e2db9030-efa5-4524-b909-9ceed52de07c
date added to LUP
2023-03-27 12:59:25
date last changed
2024-04-18 20:20:49
@article{e2db9030-efa5-4524-b909-9ceed52de07c,
  abstract     = {{<p>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).</p><p>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).</p><p>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.</p><p>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.</p>}},
  author       = {{Backman, Max and Strell, Carina and Lindberg, Amanda and Mattsson, Johanna S M and Elfving, Hedvig and Brunnström, Hans and O'Reilly, Aine and Bosic, Martina and Gulyas, Miklos and Isaksson, Johan and Botling, Johan and Kärre, Klas and Jirström, Karin and Lamberg, Kristina and Pontén, Fredrik and Leandersson, Karin and Mezheyeuski, Artur and Micke, Patrick}},
  issn         = {{0959-8049}},
  language     = {{eng}},
  pages        = {{40--52}},
  publisher    = {{Elsevier}},
  series       = {{European Journal of Cancer}},
  title        = {{Spatial immunophenotyping of the tumour microenvironment in non-small cell lung cancer}},
  url          = {{http://dx.doi.org/10.1016/j.ejca.2023.02.012}},
  doi          = {{10.1016/j.ejca.2023.02.012}},
  volume       = {{185}},
  year         = {{2023}},
}