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Methionine restriction-induced sulfur deficiency impairs antitumour immunity partially through gut microbiota. | LitMetric

AI Article Synopsis

  • - Methionine restriction (MR) shows potential in slowing cancer growth and enhancing treatment effects, but its impact on cancer progression with a functioning immune system is unclear.
  • - In healthy mice, MR actually reduces T cell levels, worsens tumor growth, and diminishes responses to immunotherapy, suggesting a complex relationship with immunity.
  • - MR leads to decreased hydrogen sulfide production by gut microbiota, crucial for immune cell health, indicating that the gut microbiome and immune system should be taken into account for any cancer-fighting benefits of MR.

Article Abstract

Restriction of methionine (MR), a sulfur-containing essential amino acid, has been reported to repress cancer growth and improve therapeutic responses in several preclinical settings. However, how MR impacts cancer progression in the context of the intact immune system is unknown. Here we report that while inhibiting cancer growth in immunocompromised mice, MR reduces T cell abundance, exacerbates tumour growth and impairs tumour response to immunotherapy in immunocompetent male and female mice. Mechanistically, MR reduces microbial production of hydrogen sulfide, which is critical for immune cell survival/activation. Dietary supplementation of a hydrogen sulfide donor or a precursor, or methionine, stimulates antitumour immunity and suppresses tumour progression. Our findings reveal an unexpected negative interaction between MR, sulfur deficiency and antitumour immunity and further uncover a vital role of gut microbiota in mediating this interaction. Our study suggests that any possible anticancer benefits of MR require careful consideration of both the microbiota and the immune system.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10513933PMC
http://dx.doi.org/10.1038/s42255-023-00854-3DOI Listing

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