scholarly journals Integrating Metagenomics into Personalized Medicine in Dermatology

2020 ◽  
Vol 4 (6) ◽  
pp. 623-625
Author(s):  
Amy Huang ◽  
Sharon Glick
Keyword(s):  
Atopic Dermatitis ◽  
Personalized Medicine ◽  
Gut Microbiome ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Therapy Response ◽  
Skin Microbiome ◽  
Metagenomic Sequencing ◽  
Microbial Composition

There has been a recent focus on the association between human microbiomes and disease development, disease resistance, and therapy response. Fecal transplants for inflammatory bowel disease and resistant Clostridium difficile infection have demonstrated that manipulating the gut microbiome can be beneficial in treating disease. Microbiomes are important in dermatology, where response to immune checkpoint inhibitors for melanoma therapy can be affected by differences in gut microbial composition. Bleach baths, which alter the skin microbiome, are known to be beneficial in atopic dermatitis. Gut dysbiosis, or disturbance in the gut microbiome in early life, can influence the development of systemic sclerosis and atopic dermatitis. Metagenomic sequencing can therefore be a useful addition to personalized medicine to identify therapy responders versus non-responders, patients at risk of serious side-effects from biologics and immune checkpoint inhibitors, and prebiotic supplements that aid in improving therapy response.

scholarly journals Gut microbiome modulates efficacy of immune checkpoint inhibitors

2018 ◽  
Vol 11 (1) ◽  
Author(s):  
Ming Yi ◽  
Shengnan Yu ◽  
Shuang Qin ◽  
Qian Liu ◽  
Hanxiao Xu ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors

IMMU-09. HUMAN MICROBIOTA INFLUENCE THE EFFICACY OF IMMUNOTHERAPY IN A MOUSE MODEL OF GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi93-vi94
Author(s):  
Kory Dees ◽  
Hyunmin Koo ◽  
James Humphreys ◽  
Joseph Hakim ◽  
David Crossman ◽  
...  
Keyword(s):  
Mouse Model ◽  
Microbial Communities ◽  
Mouse Models ◽  
Gut Microbiome ◽  
Positive Response ◽  
Checkpoint Inhibitors ◽  
Metagenomic Sequencing ◽  
Sequencing Data ◽  
Microbial Composition ◽  
Healthy Human

Abstract Although immunotherapy works well in glioblastoma (GBM) pre-clinical mouse models, the therapy has unfortunately not demonstrated efficacy in humans. In melanoma and other cancers, the composition of the gut microbiome has been shown to determine responsiveness or resistance to immune checkpoint inhibitors (anti-PD-1). Most pre-clinical cancer studies have been done in mouse models using mouse gut microbiomes, but there are significant differences between mouse and human microbial gut compositions. To address this inconsistency, we developed a novel humanized microbiome (HuM) model to study the response to immunotherapy in a pre-clinical mouse model of GBM. We used five healthy human donors for fecal transplantation of gnotobiotic mice. After the transplanted microbiomes stabilized, the mice were bred to generate five independent humanized mouse lines (HuM1-HuM5). Analysis of shotgun metagenomic sequencing data from fecal samples revealed a unique microbiome with significant differences in diversity and microbial composition among HuM1-HuM5 lines. Interestingly, we found that the HuM lines responded differently to anti-PD-1. Specifically, we demonstrate that HuM2 and HuM3 mice are responsive to anti-PD-1 and displayed significantly increased survival compared to isotype controls, while HuM1, HuM4, and HuM5 mice are resistant to anti-PD-1. These mice are genetically identical, and only differ in the composition of the gut microbiome. In a correlative experiment, we found that disrupting the responder HuM2 microbiome with antibiotics abrogated the positive response to anti-PD-1, indicating that HuM2 microbiota must be present in the mice to elicit the positive response to anti-PD-1 in the GBM model. The question remains of whether the “responsive” microbial communities in HuM2 and HuM3 can be therapeutically exploited and applicable in other tumor models, or if the “resistant” microbial communities in HuM1, HuM4, and HuM5 can be depleted and/or replaced. Future studies will assess responder microbial transplants as a method of enhancing immunotherapy.

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

2021 ◽  
Author(s):  
Ghada Araji ◽  
Julian Maamari ◽  
Fatima Ali Ahmad ◽  
Rana Zareef ◽  
Patrick Chaftari ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Therapeutic Interventions ◽  
The Impact ◽  
The Relationship ◽  
Gut Microbiota Composition

ABSTRACT The discovery of immune checkpoint inhibitors (ICIs) has revolutionized the care of cancer patients. However, the response to ICI therapy exhibits substantial interindividual variability. Efforts have been directed to identify biomarkers that predict the clinical response to ICIs. In recent years, the gut microbiome has emerged as a critical player that influences the efficacy of immunotherapy. An increasing number of studies have suggested that the baseline composition of a patient's gut microbiota and its dysbiosis are correlated with the outcome of cancer immunotherapy. This review tackles the rapidly growing body of evidence evaluating the relationship between the gut microbiome and the response to ICI therapy. Additionally, this review highlights the impact of antibiotic-induced dysbiosis on ICI efficacy and discusses the possible therapeutic interventions to optimize the gut microbiota composition to augment immunotherapy efficacy.

scholarly journals The gut microbiome and response to immune checkpoint inhibitors: preclinical and clinical strategies

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Jun Gong ◽  
Alexander Chehrazi‐Raffle ◽  
Veronica Placencio‐Hickok ◽  
Michelle Guan ◽  
Andrew Hendifar ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Clinical Strategies

scholarly journals Hepatocellular Carcinoma Immunotherapy and the Potential Influence of Gut Microbiome

2021 ◽  
Vol 22 (15) ◽  
pp. 7800
Author(s):  
Sally Temraz ◽  
Farah Nassar ◽  
Firas Kreidieh ◽  
Deborah Mukherji ◽  
Ali Shamseddine ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Critical Role ◽  
Hepatic Carcinogenesis ◽  
Host Metabolism

Disruptions in the human gut microbiome have been associated with a cycle of hepatocyte injury and regeneration characteristic of chronic liver disease. Evidence suggests that the gut microbiota can promote the development of hepatocellular carcinoma through the persistence of this inflammation by inducing genetic and epigenetic changes leading to cancer. As the gut microbiome is known for its effect on host metabolism and immune response, it comes as no surprise that the gut microbiome may have a role in the response to therapeutic strategies such as immunotherapy and chemotherapy for liver cancer. Gut microbiota may influence the efficacy of immunotherapy by regulating the responses to immune checkpoint inhibitors in patients with hepatocellular carcinoma. Here, we review the mechanisms by which gut microbiota influences hepatic carcinogenesis, the immune checkpoint inhibitors currently being used to treat hepatocellular carcinoma, as well as summarize the current findings to support the potential critical role of gut microbiome in hepatocellular carcinoma (HCC) immunotherapy.

Impact of Proton Pump Inhibitor Use on the Effectiveness of Immune Checkpoint Inhibitors in Advanced Cancer Patients

2021 ◽  
pp. 106002802110339
Author(s):  
Kangning Peng ◽  
Ken Chen ◽  
Benjamin A. Teply ◽  
Gary C. Yee ◽  
Paraskevi A. Farazi ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Cancer Patients ◽  
Advanced Cancer ◽  
Proton Pump ◽  
Gut Microbiome ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Critical Role ◽  
The Impact

Background: The gut microbiome plays a critical role in modulating the therapeutic effect of immune checkpoint inhibitors (ICIs). Proton pump inhibitors (PPIs) are commonly used in cancer patients and may affect the gut microbiome by altering gut pH. Objective: To evaluate if concurrent use of PPI is associated with overall survival (OS) and progression-free survival (PFS) in patients with stage IV non–small-cell lung cancer (NSCLC), melanoma, renal cell carcinoma, transitional cell carcinoma, or head and neck squamous cell carcinoma. Methods: This was a single-center retrospective cohort study of advanced cancer adult patients who received nivolumab or pembrolizumab between September 1, 2014, and August 31, 2019. Concomitant PPI exposure was defined as PPI use 0 to 30 days before or after initiation of ICIs. Treatment outcome was OS and PFS. Results: A total of 233 patients were included in our study. Concomitant PPI use was not significantly associated with OS (hazard ratio [HR] = 1.22; 95% CI = 0.80-1.86) or PFS (HR = 1.05; 95% CI = 0.76-1.45) in patients with ICI use. The effect estimates were robust after adjusting for covariates in multivariate analysis and in patients with NSCLC. Conclusion and Relevance: Concomitant PPI use was not associated with the effectiveness of nivolumab or pembrolizumab. Certain predictors of survival outcomes related to PPI use in patients receiving immunotherapy, such as the time window and indication of PPI exposure and autoimmune disorders, should be explored in the future to better carve out the impact of PPI on the effectiveness of ICI use.

Nanobyte

2018 ◽  
Vol 3 (1) ◽  
pp. 1
Author(s):  
Radhika A. Vaishnav
Keyword(s):  
Clinical Trials ◽  
Gut Microbiome ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Poor Responders ◽  
Microbiome Composition ◽  
Near Future ◽  
Immune Checkpoint Blockers

Immune checkpoint inhibitors targeting PD-1/PD-L1 can have differing effects in various individuals. Recent studies published have suggested a role in the gut microbiome composition in contributing to the efficacy of these drugs. Patients who took antibiotics showed a poorer response to PD-1 inhibitors compared to those who did not take any antibiotics. In another study, fecal transplants to mice from patients that improved on PD-1 blockers showed improvement on the drugs, while mice receiving transplants from poor responders showed similar lack of efficacy of PD-1 blockers. New clinical trials and metagenomics studies are anticipated in the near future that could allow us to understand better the mechanisms of the gut microbial role in the effectiveness of immune checkpoint blockers.

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