Increased Response to Immune Checkpoint Inhibitors with Dietary Methionine Restriction

Morehead, Lauren C.; Garg, Sarita; Wallis, Katherine F.; Siegel, Eric R.; Tackett, Alan J.; Miousse, Isabelle R.

doi:10.2139/ssrn.4329452

Cited by 7 publications

(4 citation statements)

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“…This was somewhat unexpected but is in good agreement with new results from our laboratory showing that methionine restriction activates immune pathways in cancer. 20 This was also reflected in the upstream analysis, where the top hits were the immune-related factors TNF, IFNG, and IL1B.…”

Section: Homocysteine Induces Hypomethylation In Both Mewo and A101d ...mentioning

confidence: 89%

Characterization of methionine dependence in melanoma cells

Garg,

Morehead,

Bird

et al. 2024

Mol. Omics

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Section: Homocysteine Induces Hypomethylation In Both Mewo and A101d ...mentioning

confidence: 89%

Characterization of methionine dependence in melanoma cells

Garg,

Morehead,

Bird

et al. 2024

Mol. Omics

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“…Dietary methionine restriction is an effective method for inducing energy loss in cancer cells and recently dietary methionine restriction combined with other treatments has shown great anti-tumour efficacy [137,138]. Cysteine and methionine deprivation sensitizes gliomas to ferroptosis, highlighting the potential for improving the efficacy of ferroptotic therapies in glioma treatment with a non-invasive dietary modification [137].…”

Section: Amino Acid Metabolism and Therapeutic Applicationsmentioning

confidence: 99%

“…Cysteine and methionine deprivation sensitizes gliomas to ferroptosis, highlighting the potential for improving the efficacy of ferroptotic therapies in glioma treatment with a non-invasive dietary modification [137]. In addition, dietary methionine restriction plus immune checkpoint inhibitors targeted against CTLA-4 and PD-1 significantly reduced tumour growth and size compared to immune checkpoint inhibitors alone [138].…”

Section: Amino Acid Metabolism and Therapeutic Applicationsmentioning

confidence: 99%

Amino acid metabolism, redox balance and epigenetic regulation in cancer

Zhang

2023

The FEBS Journal

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Amino acids act as versatile nutrients driving cell growth and survival, especially in cancer cells. Amino acid metabolism comprises numerous metabolic networks and is closely linked with intracellular redox balance and epigenetic regulation. Reprogrammed amino acid metabolism has been recognized as a ubiquitous feature in tumour cells. This review outlines the metabolism of several primary amino acids in cancer cells and highlights the pivotal role of amino acid metabolism in sustaining redox homeostasis and regulating epigenetic modification in response to oxidative and genetic stress in cancer cells.

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“…Moreover, normal (> 30 ng/dL) vitamin D3 levels, whether naturally-occurring or through oral supplementation, were associated with significantly better outcomes ( 115 ). Furthermore, experimental evidence suggests an impact of ketogenic (low carbohydrate, low protein, and high fat) diet, of dietary amino-acid restriction and of polyphenols administration on ICI efficacy ( 116 – 118 ).…”

Section: The Circadian Timing Systemmentioning

confidence: 99%

Circadian lifestyle determinants of immune checkpoint inhibitor efficacy

Hughes,

Shanaz,

Ismail-Sutton

et al. 2023

Front. Oncol.

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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.

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Increased Response to Immune Checkpoint Inhibitors with Dietary Methionine Restriction

Cited by 7 publications

References 0 publications

Characterization of methionine dependence in melanoma cells

Characterization of methionine dependence in melanoma cells

Amino acid metabolism, redox balance and epigenetic regulation in cancer

Circadian lifestyle determinants of immune checkpoint inhibitor efficacy

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