The interplay between cholesterol (and other metabolic conditions) and immune-checkpoint immunotherapy: shifting the concept from the inflamed tumor to the inflamed patient

The predictive ability of metabolic conditions, such as hypercholesterolemia, on the outcome of cancer patients to immune-checkpoint inhibitors (ICIs) therapy, has been recently explored. The reasons for their value in this setting are to be searched in the individual himself more than in his tumor, as the target of the immune-checkpoint blockade is the immune system. The efficacy of ICIs on the tumor may be based on two simple premises: 1) the physiological immune function has been blocked, and 2) the tumor progression (mainly) depends on this block. The metabolic syndrome may represent the epiphenomenon of an inflamed patient, no longer able of physiological functions required to prevent chronic inflammatory events. The metabolic dysfunction could represent merely a biomarker of the patient who satisfies both the two premises reported above. Suggestions from preclinical and translational researches should be transferred in the clinical setting, implementing randomized clinical trials with observational endpoints such as the effect of concomitant drug medications and the impact of blood cholesterol levels and other metabolic conditions on the outcome of ICI treatment.

Automated summary

Metabolic conditions like hypercholesterolemia are being explored for their predictive ability on cancer patients' response to immune-checkpoint inhibitors (ICIs) therapy. The efficacy of ICIs on tumors is based on blocking immune function and metabolic syndrome may represent an inflamed patient's inability to prevent chronic inflammatory events, potentially impacting the outcome of ICI treatment.