The heightened importance of the microbiome in cancer immunotherapy

Villemin, Clélia; Six, Anne; Neville, Bridget A.; Lawley, Trevor D.; Robinson, Matthew; Bakdash, G.

doi:10.1016/j.it.2022.11.002

Cited by 42 publications

(18 citation statements)

References 105 publications

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“…The interplay between diet, microbiome, and the immune system is increasingly recognized as an important component of immunity, including to cancer (51)(52)(53). Studies in mice and humans have shown that gut commensals influence anticancer immune responses and affect the efficacy of immune checkpoint blockade therapy (54)(55)(56)(57)(58)(59)(60).…”

Section: Discussionmentioning

confidence: 99%

Vitamin D regulates microbiome-dependent cancer immunity

Giampazolias,

Pereira da Costa,

Lam

et al. 2024

Science

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A role for vitamin D in immune modulation and in cancer has been suggested. In this work, we report that mice with increased availability of vitamin D display greater immune-dependent resistance to transplantable cancers and augmented responses to checkpoint blockade immunotherapies. Similarly, in humans, vitamin D–induced genes correlate with improved responses to immune checkpoint inhibitor treatment as well as with immunity to cancer and increased overall survival. In mice, resistance is attributable to the activity of vitamin D on intestinal epithelial cells, which alters microbiome composition in favor of Bacteroides fragilis , which positively regulates cancer immunity. Our findings indicate a previously unappreciated connection between vitamin D, microbial commensal communities, and immune responses to cancer. Collectively, they highlight vitamin D levels as a potential determinant of cancer immunity and immunotherapy success.

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Section: Discussionmentioning

confidence: 99%

Vitamin D regulates microbiome-dependent cancer immunity

Giampazolias,

Pereira da Costa,

Lam

et al. 2024

Science

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“…Lastly, with the dawn of patient derived organoids and microfluidic explant models, opportunities exist to more faithfully study different parts of the intestine as well as explore genetic, epigenetic, immune and microbiome variations in the population. Further, as gut microbiome composition has been linked to treatment efficacy, 219 such as for cancer immunotherapy; 220 development of robust personalised gut-immune-microbiome models could be key resources for predicting efficacy and improving treatments across different conditions.…”

Section: Author Contributionsmentioning

confidence: 99%

Lab-on-chip technologies for exploring the gut–immune axis in metabolic disease

Wheeler,

Stoeger,

Owens

2024

Lab Chip

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“…Several evidence reported a correlation between the Kyn/Trp circulating levels and survival in different types of cancer. Importantly, data that has been recently reviewed [27] regarding patients affected by melanoma and renal cell carcinoma receiving nivolumab (PD-1 immune checkpoint blockade) and the levels of circulating Kyn/Trp. Interestingly, increased Kyn/Trp circulating levels during treatment were associated with worse overall survival [27].…”

Section: Tryptophan Metabolism and Clinical Outcomesmentioning

confidence: 99%

“…Importantly, data that has been recently reviewed [27] regarding patients affected by melanoma and renal cell carcinoma receiving nivolumab (PD-1 immune checkpoint blockade) and the levels of circulating Kyn/Trp. Interestingly, increased Kyn/Trp circulating levels during treatment were associated with worse overall survival [27]. Also, a study conducted on stage III nonsmall cell lung cancer treated with chemo-radiotherapy has shown that high levels of Kyn/Trp before starting treatment was associated to increased lung toxicity associated with radiotherapy, suggesting a possible association between IDO activity and acute inflammatory status related to the anticancer treatment [28].…”

Section: Tryptophan Metabolism and Clinical Outcomesmentioning

confidence: 99%

Tryptophan metabolism and kynurenine metabolites in cancer: systemic nutritional and metabolic implications

Molfino,

Imbimbo,

Gallicchio

et al. 2024

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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Purpose of review To describe the role of Tryptophan (Trp) metabolism and Kynurenine (Kyn) metabolites in nutritional and metabolic changes in cancer. Recent findings Trp is in part utilized for protein and neurotransmitters biosynthesis, but more than 95% is implicated in Kyn pathways. In this molecular cascade, metabolites are produced with distinct biological activities regulating the immune response and neurotransmission with potential implications in malnutrition/cachexia during cancer. Immune dysfunction is a phenomenon occurring during cancer and malnutrition. Kyn metabolites regulate lymphocytes activity and recent data in animals showed that the inhibition of indoleamine-2,3-dioxygenase (IDO) via 1-methyl-tryptophan determines partial amelioration of inflammation, but no positive effects on the preservation of muscularity were observed. Kynurenines seem to contribute to muscle catabolism via NAD+ biosynthesis and ROS generation. Trp metabolism via the serotonin biosynthesis is involved in appetite control in cancer. Moreover, kynurenines have a role in determining fatigue in conditions associated with inflammation. Summary Trp metabolism has implications in immune and energy balance in cancer. The modulation of Trp and kynurenines have impact on central nervous system mechanisms, including appetite, fatigue, and muscle wasting/cachexia. Research focusing on these clinical implications will open new scenario for therapeutic interventions aimed at counteracting nutritional derangements in cancer.

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The heightened importance of the microbiome in cancer immunotherapy

Cited by 42 publications

References 105 publications

Vitamin D regulates microbiome-dependent cancer immunity

Vitamin D regulates microbiome-dependent cancer immunity

Lab-on-chip technologies for exploring the gut–immune axis in metabolic disease

Tryptophan metabolism and kynurenine metabolites in cancer: systemic nutritional and metabolic implications

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