The Emerging Role of the Gut Microbiome in the Cancer Response to Immune Checkpoint Inhibitors: A Narrative Review

Araji, Ghada; Maamari, Julian; Faraz, Ahmad; Zareef, Rana; Chaftari, Patrick; Yeung, Sai‐Ching Jim

doi:10.36401/jipo-21-10

Cited by 6 publications

(3 citation statements)

References 109 publications

(175 reference statements)

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“… 79 Moreover, different reviews provided insight into the potential of novel cancer therapies such as immunotherapy, CAR-T cells, and CDk-7 inhibitors in the treatment of oncological diseases. 80 – 83 As for hematological diseases, one retrospective multicenter observational study confirmed that Eltrombopag, a medication used to treat thrombocytopenia and severe aplastic anemia may be used as second- or third-line therapy in pediatric patients with chronic and refractory idiopathic thrombocytopenia. 84 Another phase 2 trial confirmed that, a new hemoglobin oxygen-affinity modulator, improves Hemoglobin levels and markers of hemolysis in pediatric patients with sickle cell disease and has the potential to mitigate sickle cell disease-related complications in patients aged ⩾4 years.…”

Section: Resultsmentioning

confidence: 99%

Identifying health research in the era of COVID-19: A scoping review

Samah

2023

SAGE Open Medicine

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Background: Health improvements are considered one of the most important fields of research. Since the coronavirus disease 2019 was declared a pandemic, it might have impacted clinical and public health research in various forms. Objectives: The goal of this study is to explore health research approaches in the era of coronavirus disease 2019. Methods: In this scoping review, we reviewed published medical full-text studies and identified potential areas of interest of health research in the era the coronavirus disease 2019 pandemic during the last 3 years within a higher educational setting. A bibliometric analysis was used to compare among published works. Results: Among the 93 studies that met the inclusion criteria, most focused on mental health ( n = 23; 24.7%). Twenty-one publications targeted coronavirus disease 2019 and its consequences on general health. Other studies have described hemato-oncological, cardiovascular, respiratory, and endocrinological diseases. 42 studies were cross-sectional or cohort studies and most of them published in Q1 journals. Almost half of them belonged to the Faculty of Medicine (49.5%) followed by the School of Arts, Sciences, and Psychology (26.9%). Conclusions: Health research has been demonstrated to be important, at all times, especially during crises. Therefore, researchers need to invest more efforts into seeking new medical updates in various health-related fields, regardless of their correlation with coronavirus disease 2019.

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Section: Resultsmentioning

confidence: 99%

Identifying health research in the era of COVID-19: A scoping review

Samah

2023

SAGE Open Medicine

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“…Similarly, Clostridium and Firmicutes have been linked to enhanced immunoregulatory responses, related to modification of the T-cell response which may directly enhance the effects of immunotherapy (Shim et al, 2023). Ruminococcus , on the other hand, has been associated with both pro– and anti-inflammatory effects, particularly related to increases in CD4+ and CD8+ T cells, potentially influencing the outcomes of immune checkpoint therapies (Araji et al, 2022). Additional recurrence-associated taxa identified in this study include Lawsonia, Bariatricus, and Blautia, the latter of which was also associated with ICB treatment outcomes in our previous pilot research (Peters et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Gut microbiome is associated with recurrence-free survival in patients with resected Stage IIIB-D or Stage IV melanoma treated with immune checkpoint inhibitors

Usyk,

Hayes,

Knight

et al. 2024

Preprint

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The gut microbiome (GMB) has been associated with outcomes of immune checkpoint blockade therapy in melanoma, but there is limited consensus on the specific taxa involved, particularly across different geographic regions. We analyzed pre-treatment stool samples from 674 melanoma patients participating in a phase-III trial of adjuvant nivolumab plus ipilimumab versus nivolumab, across three continents and five regions. Longitudinal analysis revealed that GMB was largely unchanged following treatment, offering promise for lasting GMB-based interventions. In region-specific and cross-region meta-analyses, we identified pre-treatment taxonomic markers associated with recurrence, including Eubacterium, Ruminococcus, Firmicutes, and Clostridium. Recurrence prediction by these markers was best achieved across regions by matching participants on GMB compositional similarity between the intra-regional discovery and external validation sets. AUCs for prediction ranged from 0.83-0.94 (depending on the initial discovery region) for patients closely matched on GMB composition (e.g., JSD ≤0.11). This evidence indicates that taxonomic markers for prediction of recurrence are generalizable across regions, for individuals of similar GMB composition.

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“…One potential reason for the varying efficacies of immune checkpoint blockade is the gut microbiome ( 8 – 10 ). Microbiome and microbiota are often used interchangeably, but the difference between the terms is that microbiome refers to “the collective genomes of microorganisms in a particular environment”, whilst microbiota refers to “the community of microorganisms themselves” ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

Intratumor microbiota as a novel potential prognostic indicator in mesothelioma

Pentimalli¹,

Krstic‐Demonacos²,

Costa³

et al. 2023

Front. Immunol.

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IntroductionDespite increased attention on immunotherapy, primarily immune checkpoint blockade, as a therapeutic approach for mesothelioma (MMe), its efficacy and tolerability remain questioned. One potential explanation for different responses to immunotherapy is the gut and intratumor microbiota; however, these remain an underexplored facet of MMe. This article highlights the cancer intratumor microbiota as a novel potential prognostic indicator in MMe.MethodsTCGA data on 86 MMe patients from cBioPortal underwent bespoke analysis. Median overall survival was used to divide patients into “Low Survivors” and “High Survivors”. Comparison of these groups generated Kaplan-Meier survival analysis, differentially expressed genes (DEGs), and identification of differentially abundant microbiome signatures. Decontamination analysis refined the list of signatures, which were validated as an independent prognostic indicator through multiple linear regression modelling and Cox proportional hazards modelling. Finally, functional annotation analysis on the list of DEGs was performed to link the data together.Results107 genera signatures were significantly associated with patient survival (positively or negatively), whilst clinical characteristic comparison between the two groups demonstrated that epithelioid histology was more common in “High Survivors” versus biphasic in “Low Survivors”. Of the 107 genera, 27 had published articles related to cancer, whilst only one (Klebsiella) had MMe-related published articles. Functional annotation analysis of the DEGs between the two groups highlighted fatty acid metabolism as the most enriched term in “High Survivors”, whilst for “Low Survivors” the enriched terms primarily related to cell cycle/division. Linking these ideas and findings together is that the microbiome influences, and is influenced by, lipid metabolism. Finally, to validate the independent prognostic value of the microbiome, multiple linear regression modelling as well as Cox proportional hazards modelling were employed, with both approaches demonstrating that the microbiome was a better prognostic indicator than patient age or stage of the cancer.DiscussionThe findings presented herein, alongside the very limited literature from scoping searches to validate the genera, highlight the microbiome and microbiota as a potentially rich source of fundamental analysis and prognostic value. Further in vitro studies are needed to elucidate the molecular mechanisms and functional links that may lead to altered survival.

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The Emerging Role of the Gut Microbiome in the Cancer Response to Immune Checkpoint Inhibitors: A Narrative Review

Cited by 6 publications

References 109 publications

Identifying health research in the era of COVID-19: A scoping review

Identifying health research in the era of COVID-19: A scoping review

Gut microbiome is associated with recurrence-free survival in patients with resected Stage IIIB-D or Stage IV melanoma treated with immune checkpoint inhibitors

Intratumor microbiota as a novel potential prognostic indicator in mesothelioma

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