Ketogenic diet enhances the anti-cancer effects of PD-L1 blockade in renal cell carcinoma.
Level 5 - mechanism / opinion, no new human data
Preclinical in vitro cell culture and in vivo rodent models
PubMed 38846490 · doi:10.3389/fendo.2024.1344891
What was done
The authors evaluated the effects of ketone bodies on cell proliferation, viability, and mitochondrial metabolism in ACHN and Renca renal cell carcinoma lines in vitro. In vivo, nude mice with ACHN xenografts and Balb/c mice with Renca grafts were fed either a standard diet or a 2:1 ketogenic diet ad libitum. To evaluate combination therapy, Balb/c mice were treated with anti-PD-L1 monoclonal antibody, and tumor growth was monitored.
What was found
In vitro, ketone body exposure was associated with a significant reduction in ACHN and Renca cell proliferation and viability, alongside increased mitochondrial respiration and biogenesis. In vivo, the ketogenic diet reduced tumor growth and up-regulated PD-L1 gene expression. In Balb/c mice, adjuvant ketogenic diet improved response to anti-PD-L1 treatment. The abstract reports no numerical values, effect sizes, or confidence intervals.
Why it matters
This study provides mechanistic preclinical evidence that ketogenic metabolic interventions may slow renal cell carcinoma progression and potentially augment response to immune checkpoint inhibition.
Limits
The findings are limited to cell cultures and rodent models, which do not directly predict efficacy or safety in human patients. The abstract omits sample sizes, quantitative growth metrics, and statistical parameters.
Cited by
- supports Published research demonstrates that PD-L1 immune checkpoint inhibitors are greatly augmented in efficacy when combined with a ketogenic diet.