Fasting-Mimicking Diets Reprogram Cancer-Associated Fibroblasts to Reverse the Immunosuppressive Tumor Microenvironment in Breast Cancer.

In a mouse model of spontaneous breast cancer, fasting-mimicking diets reprogram cancer-associated fibroblasts by reducing the iCAF subset and boosting NK and effector CD8+ T-cell infiltration.

• Why it matters: The tumor microenvironment often becomes immunosuppressive, limiting anti-tumor immunity; defining how fasting-mimicking diets reshape specific stromal and immune cell states could guide better combinations.
• What they did: Using single-cell transcriptomic sequencing, the study mapped TME changes after FMD and linked them mechanistically to reduced tumor-cell PDGFC secretion via glucose reduction and glycolysis inhibition, lowering JAK/STAT3-driven iCAF differentiation.
• The result: FMD plus PDGFR inhibitors increased the efficacy of anti-PD-L1 immunotherapy in vivo, supporting metabolic-immune rewiring as a basis for preliminary combination strategies in breast cancer.

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