Cell metabolism, 2020-01, Vol.31 (1), p.148-161.e5
2020
Details
- Autor(en) / Beteiligte
- Titel
- STAT3 Activation-Induced Fatty Acid Oxidation in CD8+ T Effector Cells Is Critical for Obesity-Promoted Breast Tumor Growth
- Ist Teil von
- Cell metabolism, 2020-01, Vol.31 (1), p.148-161.e5
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- Elsevier ScienceDirect Journals Complete
- Beschreibungen/Notizen
- Although obesity is known to be critical for cancer development, how obesity negatively impacts antitumor immune responses remains largely unknown. Here, we show that increased fatty acid oxidation (FAO) driven by activated STAT3 in CD8+ T effector cells is critical for obesity-associated breast tumor progression. Ablating T cell Stat3 or treatment with an FAO inhibitor in obese mice spontaneously developing breast tumor reduces FAO, increases glycolysis and CD8+ T effector cell functions, leading to inhibition of breast tumor development. Moreover, PD-1 ligation in CD8+ T cells activates STAT3 to increase FAO, inhibiting CD8+ T effector cell glycolysis and functions. Finally, leptin enriched in mammary adipocytes and fat tissues downregulates CD8+ T cell effector functions through activating STAT3-FAO and inhibiting glycolysis. We identify a critical role of increased oxidation of fatty acids driven by leptin and PD-1 through STAT3 in inhibiting CD8+ T effector cell glycolysis and in promoting obesity-associated breast tumorigenesis. [Display omitted] •STAT3 in CD8+ T effector cells upregulates FAO while inhibiting glycolysis and IFNγ•PD-1 increases FAO and inhibits IFNγ through activating STAT3 in tumor CD8+ T cells•Leptin associated with increased fat tissues activates STAT3 in CD8+ T effector cells•Blocking leptin-STAT3-FAO pathway reactivates breast tumor CD8+ T cells Obesity contributes to cancer development, but the underlying mechanisms are not well understood. Zhang and Yue et al. show that a leptin-STAT3 axis increases oxidation of fatty acids within CD8+ effector T cells in breast cancer, leading to inhibition of antitumor immune responses. Blocking STAT3 or fatty acid oxidation increases CD8+ T cell glycolysis and antitumor function.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1550-4131eISSN: 1932-7420DOI: 10.1016/j.cmet.2019.10.013Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6949402
- Format
- –
- Schlagworte
- Adipocytes - metabolism, Adipose Tissue - metabolism, Animals, Breast Neoplasms - immunology, Breast Neoplasms - metabolism, Carcinogenesis - genetics, Carcinogenesis - immunology, Carcinogenesis - metabolism, CD8 T cells, CD8-Positive T-Lymphocytes - immunology, CD8-Positive T-Lymphocytes - metabolism, Cell Line, Cell Proliferation - genetics, Chromatin Immunoprecipitation, FAO, Fatty Acids - metabolism, Female, Glycolysis - genetics, Glycolysis - physiology, Humans, IFNγ, Interferon-gamma - metabolism, leptin, Leptin - metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Middle Aged, obesity, Obesity - immunology, Obesity - metabolism, Oxidation-Reduction - drug effects, PD-1, Programmed Cell Death 1 Receptor - metabolism, PyMT model, STAT3, STAT3 Transcription Factor - genetics, STAT3 Transcription Factor - metabolism, tumor