Antibiotic-Related Changes in Microbiome: The Hidden Villain behind Colorectal Carcinoma Immunotherapy Failure

Velikova, Tsvetelina; Krastev, Boris; Lozenov, Stefan; Gencheva, Radostina; Peshevska-Sekulovska, Monika; Georgiev, G.; Peruhova, Milena

doi:10.3390/ijms22041754

Cited by 21 publications

(18 citation statements)

References 44 publications

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“…In this context, some microorganisms seem to interfere with host cell proliferation and apoptosis, tissue inflammation, cell invasion, immune system function, gene expression, oncogenic signalling, mutagenesis, angiogenesis, and hormonal and detoxification pathways (10,19,20). In addition, human microbiota's composition also influences drug disposition, action and toxicity, including of ICI (10,(21)(22)(23).…”

Section: Gut Microbiota and The Breast-gut-axismentioning

confidence: 99%

Human Microbiota and Immunotherapy in Breast Cancer - A Review of Recent Developments

et al. 2022

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Breast cancer (BC) is the most common malignancy and the second cause of cancer-specific death in women from high-income countries. Infectious agents are the third most important risk factor for cancer incidence after tobacco and obesity. Dysbiosis emerged as a key player that may influence cancer development, treatment, and prognosis through diverse biological processes. Metastatic BC has a highly variable clinical course, and more recently, immune checkpoint inhibitors (ICIs) have become an emerging therapy in BC. Even with standardised treatment protocols, patients do not respond similarly, reflecting each individual´s heterogeneity, unique BC features, and tumour microenvironment. However, there is insufficient data regarding predictive factors of response to available treatments for BC. The microbiota could be a crucial piece of the puzzle to anticipate better individual BC risk and prognosis, pharmacokinetics, pharmacodynamics, and clinical efficacy. In recent years, it has been shown that gut microbiota may modulate cancer treatments’ efficacy and adverse effects, and it is also apparent that both cancer itself and anticancer therapies interact with gut microbiota bidirectionally. Moreover, it has been proposed that certain gut microbes may protect the host against inappropriate inflammation and modulate the immune response. Future clinical research will determine if microbiota may be a prognostic and predictive factor of response to ICI and/or its side effects. Also, modulation of microbiota can be used to improve outcomes in BC patients. In this review, we discuss the potential implications of metabolomics and pharmacomicrobiomics that might impact BC immunotherapy treatment.

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Section: Gut Microbiota and The Breast-gut-axismentioning

confidence: 99%

Human Microbiota and Immunotherapy in Breast Cancer - A Review of Recent Developments

et al. 2022

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“…There is some evidence that the microbes may also alter drug metabolism. 51 Researchers have begun to analyze commensal microbiota in stool samples to identify stool signatures in various cancers and their relation to response to ICIs. 52 In one recent review, 10 studies evaluating patients with various cancer types examined the effects of the gut microbiome on clinical outcomes of ICI and related toxicity.…”

Section: The Microbiome and Solid Cancers: A New Adventure Worldmentioning

confidence: 99%

“… 58 The most significant correlation was shown by Akkermansia muciniphila and was validated across multiple cohorts. 51 Akkermansia recruits CD4+ cells and dendritic cells, mediated by IL-12. In a review by Cimadamore et al .…”

Section: The Microbiome and Rcc: Time For Loaded Gunsmentioning

confidence: 99%

The role of gut microbiome in immune modulation in metastatic renal cell carcinoma

2022

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Treatment of metastatic renal cell carcinomas (mRCC) has drastically improved since the advent of immunotherapy with immune checkpoint inhibitors (ICIs), with a significant proportion of patients achieving durable responses. While this has revolutionized treatment and improved outcomes for mRCC patients, a large subset of patients still does not respond to treatment with ICIs. Moreover, ICIs can induce various immune-related adverse events, limiting their use in many patients. Therefore, there is a need to identify the predictive biomarkers of both efficacy and toxicity associated with ICIs, which would allow for a more personalized approach and help with clinical decision-making. This review aims to explore the role of the gut microbiome in RCC to overcome primary resistance and predict response to treatment with ICIs. First, current therapeutic strategies and mechanisms of action of ICI therapies for RCC treatment will be reviewed. With the technological development of shotgun whole-genome sequencing, the gut microbiome has emerged as an exciting field of research within oncology. Thus, the role of the microbiome and its bidirectional interaction with ICIs and other drugs will be explored, with a particular focus on the microbiome profile in RCC. Lastly, the rationale for future clinical interventions to overcome resistance to ICIs using fecal microbiota transplantation in patients with RCC will be presented.

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“…The influence of the gut microbiota on immune system makes it a pivotal part of the tumor organismal environment, which largely affects the sensitivity of tumors to various treatments, especially immunotherapy [ 24 , 52 – 57 ]. The composition of intestinal microbiome has a significant impact on the efficacy of anticancer immune surveillance, which contributes to the therapeutic activity of CTLA-4 or PD-1/PD-L1-based cancer immunotherapy.…”

Section: Intestinal Microbiota and Tumor Immunotherapymentioning

confidence: 99%

The Role of Gut Microbiota in Tumor Immunotherapy

Bai

et al. 2021

Journal of Immunology Research

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Tumor immunotherapy is the fourth therapy after surgery, chemotherapy, and radiotherapy. It has made great breakthroughs in the treatment of some epithelial tumors and hematological tumors. However, its adverse reactions are common or even more serious, and the response rate in some solid tumors is not satisfactory. With the maturity of genomics and metabolomics technologies, the effect of intestinal microbiota in tumor development and treatment has gradually been recognized. The microbiota may affect tumor immunity by regulating the host immune system and tumor microenvironment. Some bacteria help fight tumors by activating immunity, while some bacteria mediate immunosuppression to help cancer cells escape from the immune system. More and more studies have revealed that the effects and complications of tumor immunotherapy are related to the composition of the gut microbiota. The composition of the intestinal microbiota that is sensitive to treatment or prone to adverse reactions has certain characteristics. These characteristics may be used as biomarkers to predict the prognosis of immunotherapy and may also be developed as “immune potentiators” to assist immunotherapy. Some clinical and preclinical studies have proved that microbial intervention, including microbial transplantation, can improve the sensitivity of immunotherapy or reduce adverse reactions to a certain extent. With the development of gene editing technology and nanotechnology, the design and development of engineered bacteria that contribute to immunotherapy has become a new research hotspot. Based on the relationship between the intestinal microbiota and immunotherapy, the correct mining of microbial information and the development of reasonable and feasible microbial intervention methods are expected to optimize tumor immunotherapy to a large extent and bring new breakthroughs in tumor treatment.

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Antibiotic-Related Changes in Microbiome: The Hidden Villain behind Colorectal Carcinoma Immunotherapy Failure

Cited by 21 publications

References 44 publications

Human Microbiota and Immunotherapy in Breast Cancer - A Review of Recent Developments

Human Microbiota and Immunotherapy in Breast Cancer - A Review of Recent Developments

The role of gut microbiome in immune modulation in metastatic renal cell carcinoma

The Role of Gut Microbiota in Tumor Immunotherapy

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