Therapeutic Time-restricted Feeding Reduces Renal Tumor Bioluminescence in Mice but Fails to Improve Anti-CTLA-4 Efficacy

Anticancer Res. 2020 Oct;40(10):5445-5456. doi: 10.21873/anticanres.14555.

Abstract

Background/aim: Dietary interventions like time-restricted feeding (TRF) show promising anti-cancer properties. We examined whether therapeutic TRF alone or combined with immunotherapy would diminish renal tumor growth in mice of varying body weights.

Materials and methods: Young (7 week) chow-fed or older (27 week) high-fat diet (HFD)-fed BALB/c mice were orthotopically injected with renal tumor cells expressing luciferase. After tumor establishment, mice were randomized to ad libitum feeding or TRF +/- anti-CTLA-4. Body composition, tumor viability and growth, and immune responses were quantified.

Results: TRF alone reduced renal tumor bioluminescence in older HFD-fed, but not young chow-fed mice. In the latter, TRF mitigated tumor-induced loss of lean- and fat-mass. However, TRF did not alter excised renal tumor weights or intratumoral immune responses and failed to improve anti-CTLA-4 outcomes in any mice.

Conclusion: Therapeutic TRF exhibits modest anti-cancer properties but fails to improve anti-CTLA-4 immune checkpoint blockade in murine renal cancer.

Keywords: Time-restricted feeding; cancer immunotherapy; high-fat diet.

MeSH terms

  • Animals
  • CTLA-4 Antigen / antagonists & inhibitors
  • CTLA-4 Antigen / immunology
  • Disease Models, Animal
  • Eating / physiology
  • Fasting*
  • Humans
  • Immunotherapy / adverse effects
  • Kidney Neoplasms / complications
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / pathology
  • Mice
  • Obesity / complications
  • Obesity / drug therapy*
  • Obesity / genetics

Substances

  • CTLA-4 Antigen
  • Ctla4 protein, mouse