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2025 ; 5
(1
): 432
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Dietary ?-3 polyunsaturated fatty acids (PUFAs) reduce cholesterol-driven
non-small cell lung cancer (NSCLC) progression in mouse models of disease
#MMPMID41131338
Harre P
; Hohenberger K
; Krammer S
; Yang Z
; Tausche P
; Willar J
; Trufa DI
; Chiriac MT
; Geppert CI
; Rauh M
; Hildner K
; Hartmann A
; Sirbu H
; Finotto S
Commun Med (Lond)
2025[Oct]; 5
(1
): 432
PMID41131338
show ga
BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of cancer
mortality, and most patients fail to respond to immune checkpoint inhibitors
(ICIs). Nutritional factors, particularly dietary lipids, influence cancer
progression and immunity. Cholesterol can promote tumor growth and immune
evasion, whereas ?-3 polyunsaturated fatty acids (PUFAs) may exert
anti-inflammatory and immunostimulatory effects. We aimed to determine how
dietary lipids influence NSCLC progression and whether ?-3 PUFA supplementation
can enhance the efficacy of PD-1 blockade. METHODS: Serum lipid profiles from 152
NSCLC patients were analyzed for associations with prognosis. Female murine NSCLC
models were fed diets enriched in cholesterol, saturated fats, or ?-3 PUFAs, with
or without anti-PD-1 therapy. Tumor growth, immune infiltration, cytokine
production, and epithelial-mesenchymal transition (EMT) markers were assessed by
flow cytometry, ELISA, and gene expression analysis. RESULTS: In patients,
elevated serum triglycerides correlate with poor outcomes, and tumor cholesterol
metabolism links to EMT marker expression. In female mice, cholesterol-rich diets
accelerate tumor growth, increase EMT-associated genes (SNAIL, Vimentin), and
elevate pro-tumoral cytokines (IL-6, IL-10, IL-17A). ?-3 PUFA diets reduce tumor
burden, lower immunosuppressive cytokines, decrease regulatory T cells, and
enhance cytotoxic T cell activity. Combining ?-3 PUFAs with anti-PD-1 therapy
synergistically suppresses tumor growth and improves antitumor immune responses.
CONCLUSIONS: Dietary lipids modulate NSCLC progression via metabolic,
inflammatory, and immune pathways. ?-3 PUFA supplementation counteracts
cholesterol-driven tumor promotion and augments PD-1 blockade efficacy,
supporting dietary modulation as a complementary strategy to improve
immunotherapy outcomes in NSCLC.