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- W4313373219 abstract "Abstract Non-small cell lung cancer (NSCLC) is the foremost cause of cancer-related mortality in the U.S. While early detection followed by surgery allows for the best possible NSCLC outcome, recurrence still occurs in 30% of these cases, and existing adjuvant therapies have largely failed to improve this statistic. Therefore, pressing need exists for more effective early stage NSCLC treatments. Metformin, a widely used diabetes drug with minimal side effects, is also known to show anti-cancer activity. A retrospective study of early and multistage NSCLC patients treated at Roswell Park revealed that the survival benefit of metformin is surprisingly restricted to overweight or obese patients with a body mass index (BMI)>25kg/m2. In line with this, murine lung cancer models showed that metformin treatment markedly slowed tumor growth in obese mice while minimally affecting normal controls. Flow cytometric analysis of tumor-infiltrating cells from obese mice revealed indications of immune dysfunction including elevated frequencies of suppressor cells and high levels of the inhibitory checkpoint molecules PD-1 and CTLA-4. Strikingly, metformin reversed these obesity-driven changes while promoting an abundance of activated, memory T cells in tumor-associated tissues. Transcriptome analysis of tumor gene expression in both mice and patients found that metformin counteracts discrete metabolic pressures brought on by obesity capable of dampening anti-tumor immune responses including altered expression of solute transporters and biosynthetic pathways. Our findings suggest that metformin has the potential to improve NSCLC treatment of high-BMI patients by reshaping obesity’s impact on tumor gene expression and anti-tumor immunity." @default.
- W4313373219 created "2023-01-06" @default.
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- W4313373219 date "2020-05-01" @default.
- W4313373219 modified "2023-10-03" @default.
- W4313373219 title "Metformin corrects immune dysfunction and modulates tumor gene expression in overweight individuals to yield context-specific improvement of lung cancer outcomes" @default.
- W4313373219 doi "https://doi.org/10.4049/jimmunol.204.supp.240.13" @default.
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