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An immune score reflecting pro- and anti-tumoural balance of tumour microenvironment has major prognostic impact and predicts immunotherapy response in solid cancers

Mezheyeuski, Artur ; Backman, Max ; Mattsson, Johanna ; Martín-Bernabé, Alfonso ; Larsson, Chatarina ; Hrynchyk, Ina ; Hammarström, Klara ; Ström, Simon ; Ekström, Joakim and Mauchanski, Siarhei , et al. (2023) In EBioMedicine 88. p.1-18
Abstract

Background: Cancer immunity is based on the interaction of a multitude of cells in the spatial context of the tumour tissue. Clinically relevant immune signatures are therefore anticipated to fundamentally improve the accuracy in predicting disease progression. Methods: Through a multiplex in situ analysis we evaluated 15 immune cell classes in 1481 tumour samples. Single-cell and bulk RNAseq data sets were used for functional analysis and validation of prognostic and predictive associations. Findings: By combining the prognostic information of anti-tumoural CD8+ lymphocytes and tumour supportive CD68+CD163+ macrophages in colorectal cancer we generated a signature of immune activation (SIA). The... (More)

Background: Cancer immunity is based on the interaction of a multitude of cells in the spatial context of the tumour tissue. Clinically relevant immune signatures are therefore anticipated to fundamentally improve the accuracy in predicting disease progression. Methods: Through a multiplex in situ analysis we evaluated 15 immune cell classes in 1481 tumour samples. Single-cell and bulk RNAseq data sets were used for functional analysis and validation of prognostic and predictive associations. Findings: By combining the prognostic information of anti-tumoural CD8+ lymphocytes and tumour supportive CD68+CD163+ macrophages in colorectal cancer we generated a signature of immune activation (SIA). The prognostic impact of SIA was independent of conventional parameters and comparable with the state-of-art immune score. The SIA was also associated with patient survival in oesophageal adenocarcinoma, bladder cancer, lung adenocarcinoma and melanoma, but not in endometrial, ovarian and squamous cell lung carcinoma. We identified CD68+CD163+ macrophages as the major producers of complement C1q, which could serve as a surrogate marker of this macrophage subset. Consequently, the RNA-based version of SIA (ratio of CD8A to C1QA) was predictive for survival in independent RNAseq data sets from these six cancer types. Finally, the CD8A/C1QA mRNA ratio was also predictive for the response to checkpoint inhibitor therapy. Interpretation: Our findings extend current concepts to procure prognostic information from the tumour immune microenvironment and provide an immune activation signature with high clinical potential in common human cancer types. Funding: Swedish Cancer Society, Lions Cancer Foundation, Selanders Foundation, P.O. Zetterling Foundation, U-CAN supported by SRA CancerUU, Uppsala University and Region Uppsala.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Immunoscore, Macrophages, Tumour immunology
in
EBioMedicine
volume
88
article number
104452
pages
1 - 18
publisher
Elsevier
external identifiers
  • pmid:36724681
  • scopus:85147117975
ISSN
2352-3964
DOI
10.1016/j.ebiom.2023.104452
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2023 The Author(s)
id
5dafa429-dfa9-42a3-8e09-97375ac0f242
date added to LUP
2023-02-06 18:42:30
date last changed
2024-04-18 18:33:27
@article{5dafa429-dfa9-42a3-8e09-97375ac0f242,
  abstract     = {{<p>Background: Cancer immunity is based on the interaction of a multitude of cells in the spatial context of the tumour tissue. Clinically relevant immune signatures are therefore anticipated to fundamentally improve the accuracy in predicting disease progression. Methods: Through a multiplex in situ analysis we evaluated 15 immune cell classes in 1481 tumour samples. Single-cell and bulk RNAseq data sets were used for functional analysis and validation of prognostic and predictive associations. Findings: By combining the prognostic information of anti-tumoural CD8<sup>+</sup> lymphocytes and tumour supportive CD68<sup>+</sup>CD163<sup>+</sup> macrophages in colorectal cancer we generated a signature of immune activation (SIA). The prognostic impact of SIA was independent of conventional parameters and comparable with the state-of-art immune score. The SIA was also associated with patient survival in oesophageal adenocarcinoma, bladder cancer, lung adenocarcinoma and melanoma, but not in endometrial, ovarian and squamous cell lung carcinoma. We identified CD68<sup>+</sup>CD163<sup>+</sup> macrophages as the major producers of complement C1q, which could serve as a surrogate marker of this macrophage subset. Consequently, the RNA-based version of SIA (ratio of CD8A to C1QA) was predictive for survival in independent RNAseq data sets from these six cancer types. Finally, the CD8A/C1QA mRNA ratio was also predictive for the response to checkpoint inhibitor therapy. Interpretation: Our findings extend current concepts to procure prognostic information from the tumour immune microenvironment and provide an immune activation signature with high clinical potential in common human cancer types. Funding: Swedish Cancer Society, Lions Cancer Foundation, Selanders Foundation, P.O. Zetterling Foundation, U-CAN supported by SRA CancerUU, Uppsala University and Region Uppsala.</p>}},
  author       = {{Mezheyeuski, Artur and Backman, Max and Mattsson, Johanna and Martín-Bernabé, Alfonso and Larsson, Chatarina and Hrynchyk, Ina and Hammarström, Klara and Ström, Simon and Ekström, Joakim and Mauchanski, Siarhei and Khelashvili, Salome and Lindberg, Amanda and Agnarsdóttir, Margrét and Edqvist, Per Henrik and Huvila, Jutta and Segersten, Ulrika and Malmström, Per-Uno and Botling, Johan and Nodin, Björn and Hedner, Charlotta and Borg, David and Brändstedt, Jenny and Sartor, Hanna and Leandersson, Karin and Glimelius, Bengt and Portyanko, Anna and Ponten, Fredrik and Jirström, Karin and Micke, Patrick and Sjöblom, Tobias}},
  issn         = {{2352-3964}},
  keywords     = {{Immunoscore; Macrophages; Tumour immunology}},
  language     = {{eng}},
  pages        = {{1--18}},
  publisher    = {{Elsevier}},
  series       = {{EBioMedicine}},
  title        = {{An immune score reflecting pro- and anti-tumoural balance of tumour microenvironment has major prognostic impact and predicts immunotherapy response in solid cancers}},
  url          = {{http://dx.doi.org/10.1016/j.ebiom.2023.104452}},
  doi          = {{10.1016/j.ebiom.2023.104452}},
  volume       = {{88}},
  year         = {{2023}},
}