Tying Small Changes to Large Outcomes: The Cautious Promise in Incorporating the Microbiome into Immunotherapy

Chau, Justin; Zhang, Jun

doi:10.3390/ijms22157900

Cited by 3 publications

(3 citation statements)

References 79 publications

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“…Several studies, including ours, have associated the gut microbiome with the host’s immune system and immunotherapy response and irAEs [ 12 , 13 , 14 , 15 , 16 ]. For example, Bacteroides thetaiotaomicron and Bacteroides fragilis were reported to be positively associated with the efficacy of CTLA-4 blockade [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Exploring Gut Microbiome in Predicting the Efficacy of Immunotherapy in Non-Small Cell Lung Cancer

Liu

Chau

Dai

et al. 2022

Cancers

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We performed various analyses on the taxonomic and functional features of the gut microbiome from NSCLC patients treated with immunotherapy to establish a model that may predict whether a patient will benefit from immunotherapy. We collected 65 published whole metagenome shotgun sequencing samples along with 14 samples from our previous study. We systematically studied the taxonomical characteristics of the dataset and used both the random forest (RF) and the multilayer perceptron (MLP) neural network models to predict patients with progression-free survival (PFS) above 6 months versus those below 3 months. Our results showed that the RF classifier achieved the highest F-score (85.2%) and the area under the receiver operating characteristic curve (AUC) (95%) using the protein families (Pfam) profile, and the MLP neural network classifier achieved a 99.9% F-score and 100% AUC using the same Pfam profile. When applying the model trained in the Pfam profile directly to predict the treatment response, we found that both trained RF and MLP classifiers significantly outperformed the stochastic predictor in F-score. Our results suggested that such a predictive model based on functional (e.g., Pfam) rather than taxonomic profile might be clinically useful to predict whether an NSCLC patient will benefit from immunotherapy, as both the F-score and AUC of functional profile outperform that of taxonomic profile. In addition, our model suggested that interactive biological processes such as methanogenesis, one-carbon, and amino acid metabolism might be important in regulating the immunotherapy response that warrants further investigation.

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Section: Introductionmentioning

confidence: 99%

Exploring Gut Microbiome in Predicting the Efficacy of Immunotherapy in Non-Small Cell Lung Cancer

Liu

Chau

Dai

et al. 2022

Cancers

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“…Possible mechanisms linking microbes and immunotherapy include the stimulation of T cells by specific bacterial antigens, which then trigger cross-reactions against tumor neoantigens. Meanwhile, bacterial toxins can also stimulate the recruitment of T cells, thereby releasing inflammatory cytokines such as IL-17, and combat immune tolerance (Chau and Zhang, 2021). IrAEs may be related to bacterial metabolites, which have proinflammatory properties.…”

Section: Environmental Factorsmentioning

confidence: 99%

PD-1/PD-L1 Inhibitors in Patients With Preexisting Autoimmune Diseases

Zhang

Kong

et al. 2022

Front. Pharmacol.

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Autoimmune diseases and malignant tumors are the two hotspots and difficulties that are currently being studied and concerned by the medical field. The use of PD-1/PD-L1 inhibitors improves the prognosis of advanced tumors, but excessive immune responses can also induce immune-related adverse events (irAEs). Due to this concern, many clinical trials exclude cancer patients with preexisting autoimmune disease (AID). This review outlines the possible mechanisms of irAE, discusses the safety and efficacy of PD-1/PD-L1 inhibitors in cancer patients with preexisting AID, and emphasizes the importance of early recognition, continuous monitoring, and multidisciplinary cooperation in the prevention and management of cancer patients with preexisting AID.

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“…Several methods have been suggested to identify specific microbiome that can alter the immune response and epigenetic pathways. Therapeutic solutions to an altered microbial composition might also be fecal transplantation as dysbiosis correction therapy (DCT) [ 99 ]. DCT could be valuable when applied in combination with IC inhibitors to improve treatment response in mesotheliomas.…”

Section: Involvement Of Microbiota As Regulators Of Immune Responsementioning

confidence: 99%

Microbiomes, Epigenomics, Immune Response, and Splicing Signatures Interplay: Potential Use of Combination of Regulatory Pathways as Targets for Malignant Mesothelioma

Damane

Mkhize‐Kwitshana

Mehrotra³

et al. 2022

IJMS

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Malignant mesotheliomas (MM) are hard to treat malignancies with poor prognosis and high mortality rates. This cancer is highly misdiagnosed in Sub-Saharan African countries. According to literature, the incidence of MM is likely to increase particularly in low-middle-income countries (LMICs). The burden of asbestos-induced diseases was estimated to be about 231,000 per annum. Lack of awareness and implementation of regulatory frameworks to control exposure to asbestos fibers contributes to the expected increase. Exposure to asbestos fibers can lead to cancer initiation by several mechanisms. Asbestos-induced epigenetic modifications of gene expression machinery and non-coding RNAs promote cancer initiation and progression. Furthermore, microbiome–epigenetic interactions control the innate and adaptive immunity causing exacerbation of cancer progression and therapeutic resistance. This review discusses epigenetic mechanisms with more focus on miRNAs and their interaction with the microbiome. The potential use of epigenetic alterations and microbiota as specific biomarkers to aid in the early detection and/or development of therapeutic targets is explored. The advancement of combinatorial therapies to prolong overall patient survival or possible eradication of MM especially if it is detected early is discussed.

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Tying Small Changes to Large Outcomes: The Cautious Promise in Incorporating the Microbiome into Immunotherapy

Cited by 3 publications

References 79 publications

Exploring Gut Microbiome in Predicting the Efficacy of Immunotherapy in Non-Small Cell Lung Cancer

Exploring Gut Microbiome in Predicting the Efficacy of Immunotherapy in Non-Small Cell Lung Cancer

PD-1/PD-L1 Inhibitors in Patients With Preexisting Autoimmune Diseases

Microbiomes, Epigenomics, Immune Response, and Splicing Signatures Interplay: Potential Use of Combination of Regulatory Pathways as Targets for Malignant Mesothelioma

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