– We used multiple ‘omic’ analyses to examine metabolic reprogramming within the tumour microenvironment (TME) in breast cancer and studied whether and how it evolves during neoadjuvant chemotherapy. We identified targetable vulnerabilities of immunometabolism with the potential to be exploited in immunotherapy combination strategies, says Theodoros Foukakis, researcher at the Department of Oncology-Pathology, Karolinska Institutet, who led the study.
The researchers discovered that changes in immune state, tumor metabolic proteins, and tumor cell gene expression are linked to treatment response. Potential drivers of immunometabolism were identified and validated in vitro, suggesting that targeting tumor metabolism could be used for immunomodulation.
Implications for future therapies
The findings underscore the potential of targeting tumor metabolism to enhance the effectiveness of immunotherapies. By understanding the dynamic relationship between tumor-intrinsic metabolic states and the tumor microenvironment, new prognostic biomarkers and therapeutic targets may emerge, paving the way for precision medicine in breast cancer treatment.
This study not only sheds light on the intricate ecosystem of breast cancer but also opens the door to novel treatment strategies that could significantly improve patient outcomes. The approach to characterize the genomic and proteomic landscape of breast cancer represents a promising direction for future cancer research and therapy.
Publication
Longitudinal molecular profiling elucidates immunometabolism dynamics in breast cancer.
Wang K, Zerdes I, Johansson HJ, Sarhan D, Sun Y, Kanellis DC, Sifakis EG, Mezheyeuski A, Liu X, Loman N, Hedenfalk I, Bergh J, Bartek J, Hatschek T, Lehtiö J, Matikas A, Foukakis T
Nat Commun 2024 May;15(1):3837