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Published on: July 24, 2018
Circadian lifestyle determinants of immune checkpoint inhibitor efficacy
Bethan R Hughes1,2, Sadiq Shanaz1, Seline Ismail-Sutton1
1Oncology Department, Ysbyty Gwynedd, Betsi Cadwaladr University Health Board, Bangor, United Kingdom.
Abstract:
Immune Checkpoint Inhibitors (ICI) have revolutionised cancer care in recent years. Despite a global improvement in the efficacy and tolerability of systemic anticancer treatments, a sizeable proportion of patients still do not benefit maximally from ICI. Extensive research has been undertaken to reveal the immune- and cancer-related mechanisms underlying resistance and response to ICI, yet more limited investigations have explored potentially modifiable lifestyle host factors and their impact on ICI efficacy and tolerability. Moreover, multiple trials have reported a marked and coherent effect of time-of-day ICI administration and patients' outcomes. The biological circadian clock indeed temporally controls multiple aspects of the immune system, both directly and through mediation of timing of lifestyle actions, including food intake, physical exercise, exposure to bright light and sleep. These factors potentially modulate the immune response also through the microbiome, emerging as an important mediator of a patient's immune system. Thus, this review will look at critically amalgamating the existing clinical and experimental evidence to postulate how modifiable lifestyle factors could be used to improve the outcomes of cancer patients on immunotherapy through appropriate and individualised entrainment of the circadian timing system and temporal orchestration of the immune system functions.
Insights
Optimizing cancer immunotherapy (ICI) involves understanding lifestyle factors. This review explores how circadian rhythms and daily habits can enhance patient response to immune checkpoint inhibitors.
Area of Science:
- Immunology
- Chronobiology
- Oncology
Background:
- Immune Checkpoint Inhibitors (ICI) have transformed cancer treatment, but many patients do not achieve maximal benefit.
- Research on ICI resistance/response primarily focuses on immune and cancer mechanisms, with less attention to modifiable lifestyle factors.
- Emerging evidence suggests time-of-day administration of ICI impacts patient outcomes.
Purpose of the Study:
- To critically review existing clinical and experimental evidence on modifiable lifestyle factors and their impact on ICI efficacy and tolerability.
- To explore the role of the circadian timing system in mediating lifestyle factors and immune responses.
- To postulate strategies for improving cancer immunotherapy outcomes through lifestyle interventions.
Main Methods:
- Systematic review and critical amalgamation of current clinical and experimental data.
- Analysis of the influence of circadian rhythms on immune system functions.
- Investigation of lifestyle factors (diet, exercise, sleep, light exposure) and their interaction with the microbiome.
Main Results:
- The circadian clock influences immune system activity and response to therapy.
- Lifestyle factors, timed according to circadian rhythms, can modulate immune responses.
- The microbiome is an emerging mediator influenced by lifestyle and potentially impacting immunotherapy.
Conclusions:
- Modifiable lifestyle factors, when aligned with circadian timing, offer a promising avenue to enhance cancer immunotherapy efficacy.
- Individualized chronotherapy and lifestyle interventions may optimize patient outcomes.
- Further research is needed to elucidate the complex interplay between circadian biology, lifestyle, microbiome, and immunotherapy.
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