More fuel for the fire: Gut microbes and toxicity to immune agonist antibodies in cancer

Chelvanambi, Manoj; Wargo, Jennifer A.

doi:10.1016/j.xcrm.2021.100482

Cited by 1 publication

(1 citation statement)

References 9 publications

(10 reference statements)

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“…Interestingly, toxicity observed with CD137 IAAs also appears to converge at the level of host MyD88 activation by gut microbiota, which results in a CD8+ T-cell-dependent liver damage and IFNγ driven systemic inflammation. Importantly, toxicity to IAA therapy was reduced in germ-free or antibiotictreated mice in this model without a deleterious impact on antitumor immunity, suggesting a potential roadmap for irAE modulation and prevention in the clinical setting [83,84].…”

Section: The Role Of Gut Microbes and Diet In Toxicitymentioning

confidence: 89%

Monitoring and Modulating Diet and Gut Microbes to Enhance Response and Reduce Toxicity to Cancer Treatment

Knisely

Seo

Wargo

et al. 2023

Cancers

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The gut microbiome comprises a diverse array of microbial species that have been shown to dynamically modulate host immunity both locally and systemically, as well as contribute to tumorigenesis. In this review, we discuss the scientific evidence on the role that gut microbes and diet play in response and toxicity to cancer treatment. We highlight studies across multiple cancer cohorts that have shown an association between particular gut microbiome signatures and an improved response to immune checkpoint blockade, chemotherapy, and adoptive cell therapies, as well as the role of particular microbes in driving treatment-related toxicity and how the microbiome can be modulated through strategies, such as fecal transplant. We also summarize the current literature that implicate high fiber and ketogenic diets in improved response rates to immunotherapy and chemotherapy, respectively. Finally, we discuss the relevance of these findings in the context of patient care, advocate for a holistic approach to cancer treatment, and comment on the next frontier of targeted gut and tumor microbiome modulation through novel therapeutics, dietary intervention, and precision-medicine approaches.

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Section: The Role Of Gut Microbes and Diet In Toxicitymentioning

confidence: 89%