Caloric restriction and fasting have been known for a long time for their health- and life-span promoting effects, with coherent observations in multiple model organisms as well as epidemiological and clinical studies. This holds particularly true for
cancer. The health-promoting effects of
caloric restriction and fasting are mediated at least partly through their cellular effects-chiefly autophagy induction-rather than reduced calorie intake per se. Interestingly,
caloric restriction has a differential impact on
cancer and healthy cells, due to the atypical metabolic profile of malignant
tumors.
Caloric restriction mimetics are non-toxic compounds able to mimic the biochemical and physiological effects of
caloric restriction including autophagy induction.
Caloric restriction and its mimetics induce autophagy to improve the efficacy of some
cancer treatments that induce immunogenic cell death (ICD), a type of cellular demise that eventually elicits adaptive antitumor immunity.
Caloric restriction and its mimetics also enhance the therapeutic efficacy of chemo-
immunotherapies combining ICD-inducing agents with
immune checkpoint inhibitors targeting PD-1. Collectively, preclinical data encourage the application of
caloric restriction and its mimetics as an adjuvant to
immunotherapies. This recommendation is subject to confirmation in additional experimental settings and in clinical trials. In this work, we review the preclinical and clinical evidence in favor of such therapeutic interventions before listing ongoing clinical trials that will shed some light on this subject.