Sistema de Salut de Catalunya
Institut Català de la Salut
[Wang k] Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. [Zerdes I] Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. Theme Cancer, Karolinska University Hospital and Karolinska Comprehensive Cancer Center, Stockholm, Sweden. [Johansson HJ] Department of Oncology-Pathology, Karolinska Institutet, and Science for Life Laboratory, Stockholm, Sweden. [Sarhan D, Sun Y] Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Stockholm, Sweden. [Kanellis DC] Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. [Mezheyeuski A] Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala, Sweden. Molecular Oncology Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2024-05-15T07:09:54Z
2024-05-15T07:09:54Z
2024-05-07
Immunometabolism; Breast cancer
Immunometabolisme; Càncer de mama
Inmunometabolismo; Cáncer de mama
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.
Open access funding provided by Karolinska Institute.
Article
Published version
English
Mama - Càncer - Aspectes genètics; Regulació genètica; Metabolisme; DISEASES::Neoplasms::Neoplasms by Site::Breast Neoplasms; Other subheadings::Other subheadings::Other subheadings::/metabolism; PHENOMENA AND PROCESSES::Cell Physiological Phenomena::Cellular Microenvironment::Tumor Microenvironment; ANATOMY::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Chemotherapy, Adjuvant; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de la mama; Otros calificadores::Otros calificadores::Otros calificadores::/metabolismo; FENÓMENOS Y PROCESOS::fenómenos fisiológicos celulares::microambiente celular::microambiente tumoral; ANATOMÍA::células::células cultivadas::línea celular::línea celular tumoral; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::quimioterapia adyuvante
Nature Research
Nature communications;15(1)
https://doi.org/10.1038/s41467-024-47932-y
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
