Abstract F3-2: Fasting and caloric restriction mimetics stimulate anticancer immunosurveillance

Abstract Fasting and caloric restriction induce metabolic and neuroendocrine changes that have major anti-inflammatory and immunostimulatory effects. Some of these effects are mediated by a raise of ketone bodies (such as 3-hydroxybutyrate) and a decrease in circulating insulin-like growth factor-1 (IGF1), meaning that administration of 3-hydroxybutyrate and pharmacological inhibition of IGF1 receptor can mimic some of the beneficial effects of fasting on anticancer immunosurveillance. "Caloric restriction mimetics" (CRMs) are small molecules that induce autophagy through the same pathways that are activated by fasting, including the reduction of cytoplasmic protein acetylation. We have accumulated evidence that CRMs can stimulate anticancer immunosurveillance either as single agents (for the prevention of malignant disease) or in combination with chemotherapy and/or immune checkpoint blockade (for the treatment of established cancers). In preclinical experiments, fasting and CRMs have also been used for the prevention or treatment of hormone-induced breast cancer, and these effects are coupled to an increase in the T lymphocyte-mediated anticancer immune response. We have developed an in vitro screening assay to identify novel pharmacological agents that act as CRMs. Such neo-CRMs can be successfully employed to improve anticancer immunosurveillance in preclinical experiments. Citation Format: Guido Kroemer. Fasting and caloric restriction mimetics stimulate anticancer immunosurveillance [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr F3-2.