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Longitudinal molecular profiling elucidates immunometabolism dynamics in breast cancer

Wang, Kang ; Zerdes, Ioannis ; Johansson, Henrik J. ; Sarhan, Dhifaf ; Sun, Yizhe ; Kanellis, Dimitris C. ; Sifakis, Emmanouil G. ; Mezheyeuski, Artur ; Liu, Xingrong and Loman, Niklas LU , et al. (2024) In Nature Communications 15(1).
Abstract

Although metabolic reprogramming within tumor cells and tumor microenvironment (TME) is well described in breast cancer, little is known about how the interplay of immune state and cancer metabolism evolves during treatment. Here, we characterize the immunometabolic profiles of tumor tissue samples longitudinally collected from individuals with breast cancer before, during and after neoadjuvant chemotherapy (NAC) using proteomics, genomics and histopathology. We show that the pre-, on-treatment and dynamic changes of the immune state, tumor metabolic proteins and tumor cell gene expression profiling-based metabolic phenotype are associated with treatment response. Single-cell/nucleus RNA sequencing revealed distinct tumor and immune... (More)

Although metabolic reprogramming within tumor cells and tumor microenvironment (TME) is well described in breast cancer, little is known about how the interplay of immune state and cancer metabolism evolves during treatment. Here, we characterize the immunometabolic profiles of tumor tissue samples longitudinally collected from individuals with breast cancer before, during and after neoadjuvant chemotherapy (NAC) using proteomics, genomics and histopathology. We show that the pre-, on-treatment and dynamic changes of the immune state, tumor metabolic proteins and tumor cell gene expression profiling-based metabolic phenotype are associated with treatment response. Single-cell/nucleus RNA sequencing revealed distinct tumor and immune cell states in metabolism between cold and hot tumors. Potential drivers of NAC based on above analyses were validated in vitro. In summary, the study shows that the interaction of tumor-intrinsic metabolic states and TME is associated with treatment outcome, supporting the concept of targeting tumor metabolism for immunoregulation.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
15
issue
1
article number
3837
publisher
Nature Publishing Group
external identifiers
  • pmid:38714665
  • scopus:85192374349
ISSN
2041-1723
DOI
10.1038/s41467-024-47932-y
language
English
LU publication?
yes
id
509f3316-c44d-4990-8e59-098abb706bcb
date added to LUP
2025-01-09 11:56:29
date last changed
2025-07-11 03:12:25
@article{509f3316-c44d-4990-8e59-098abb706bcb,
  abstract     = {{<p>Although metabolic reprogramming within tumor cells and tumor microenvironment (TME) is well described in breast cancer, little is known about how the interplay of immune state and cancer metabolism evolves during treatment. Here, we characterize the immunometabolic profiles of tumor tissue samples longitudinally collected from individuals with breast cancer before, during and after neoadjuvant chemotherapy (NAC) using proteomics, genomics and histopathology. We show that the pre-, on-treatment and dynamic changes of the immune state, tumor metabolic proteins and tumor cell gene expression profiling-based metabolic phenotype are associated with treatment response. Single-cell/nucleus RNA sequencing revealed distinct tumor and immune cell states in metabolism between cold and hot tumors. Potential drivers of NAC based on above analyses were validated in vitro. In summary, the study shows that the interaction of tumor-intrinsic metabolic states and TME is associated with treatment outcome, supporting the concept of targeting tumor metabolism for immunoregulation.</p>}},
  author       = {{Wang, Kang and Zerdes, Ioannis and Johansson, Henrik J. and Sarhan, Dhifaf and Sun, Yizhe and Kanellis, Dimitris C. and Sifakis, Emmanouil G. and Mezheyeuski, Artur and Liu, Xingrong and Loman, Niklas and Hedenfalk, Ingrid and Bergh, Jonas and Bartek, Jiri and Hatschek, Thomas and Lehtiö, Janne and Matikas, Alexios and Foukakis, Theodoros}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Longitudinal molecular profiling elucidates immunometabolism dynamics in breast cancer}},
  url          = {{http://dx.doi.org/10.1038/s41467-024-47932-y}},
  doi          = {{10.1038/s41467-024-47932-y}},
  volume       = {{15}},
  year         = {{2024}},
}