Microbiome transplantation and modulation of immune related adverse events.
Ontology highlight
ABSTRACT:
SUBMITTER: Smibert OC
PROVIDER: S-EPMC6537550 | biostudies-literature | 2019 Feb
REPOSITORIES: biostudies-literature
Publications
Microbiome transplantation and modulation of immune related adverse events.
Smibert Olivia C OC Guo Christina W CW Khoo Chloe C Thursky K A KA Sandhu Shahneen S Slavin Monica A MA
EClinicalMedicine 20190201
Similar Datasets
Project description:Checkpoint inhibitors are part of the family of immunotherapies and are increasingly being used in a wide variety of cancers. Immune-related adverse events pose a major challenge in the treatment of cancer patients. Pneumonitis is a rare immune-related adverse event that presents in distinct patterns. The goal of this chapter is to instruct readers on the incidence and clinical manifestations of pneumonitis and to offer guidance in the evaluation and treatment of patients with pneumonitis.
| S-EPMC7161534 | biostudies-literature
Project description:Systemic treatment options for patients with lung cancer have expanded in recent years, with a number of immunotherapeutic strategies now in our treatment armamentarium. Toxicity of and resistance to treatment hold a major stake in lung cancer morbidity and mortality. Herein, we summarise the background, current evidence and potential mechanisms underlying the role of the commensal gut microbiota in immunotherapy outcomes such as response and toxicity in patients with non-small cell lung cancer (NSCLC).
| S-EPMC9388426 | biostudies-literature
Project description:BackgroundDespite providing clinical benefit, immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) in a number of patients. This study explored the development pattern in irAEs research from a bibliometric perspective.MethodsWe obtained articles and reviews related to irAEs from the Web of Science Core Collection (WoSCC) (retrieved on September 13, 2022). Using the R package "Bibliometrix", the main bibliometric features were calculated, and a three-filed plot was generated to show the relationship between authors, institutions, and topics. VOSviewer was used for co-authorship and keyword co-occurrence analysis and visualization. CiteSpace was used to detect burst references and keywords.ResultsA total of 3995 publications on irAEs were included. The United States (US), Japan, and China had the highest publications. The Journal for ImmunoTherapy of Cancer had the highest number of publications. In addition to "immune-related adverse events", "immune checkpoint inhibitors", "immunotherapy", and "nivolumab" were the most frequently used keywords.ConclusionsA bibliometric analysis of 17 years of irAEs research was conducted to map a basic knowledge structure including countries, institutions, authors, journals, and publications. The findings provided a comprehensive perspective on the broad future of this research area.
| S-EPMC9797501 | biostudies-literature
Project description:BackgroundThe impact of the gut microbiome on the initiation and intensity of immune-related adverse events (irAEs) prompted by immune checkpoint inhibitors (ICIs) is widely acknowledged. Nevertheless, there is inconsistency in the gut microbial associations with irAEs reported across various studies.MethodsWe performed a comprehensive analysis leveraging a dataset that included published microbiome data (n = 317) and in-house generated data from 16S rRNA and shotgun metagenome samples of irAEs (n = 115). We utilized a machine learning-based approach, specifically the Random Forest (RF) algorithm, to construct a microbiome-based classifier capable of distinguishing between non-irAEs and irAEs. Additionally, we conducted a comprehensive analysis, integrating transcriptome and metagenome profiling, to explore potential underlying mechanisms.ResultsWe identified specific microbial species capable of distinguishing between patients experiencing irAEs and non-irAEs. The RF classifier, developed using 14 microbial features, demonstrated robust discriminatory power between non-irAEs and irAEs (AUC = 0.88). Moreover, the predictive score from our classifier exhibited significant discriminative capability for identifying non-irAEs in two independent cohorts. Our functional analysis revealed that the altered microbiome in non-irAEs was characterized by an increased menaquinone biosynthesis, accompanied by elevated expression of rate-limiting enzymes menH and menC. Targeted metabolomics analysis further highlighted a notably higher abundance of menaquinone in the serum of patients who did not develop irAEs compared to the irAEs group.ConclusionsOur study underscores the potential of microbial biomarkers for predicting the onset of irAEs and highlights menaquinone, a metabolite derived from the microbiome community, as a possible selective therapeutic agent for modulating the occurrence of irAEs.
| S-EPMC10799412 | biostudies-literature
Project description:The advent of novel, innovative, and effective anti-cancer immunotherapies has engendered an era of renewed optimism among cancer specialists and their patients. Foremost among these successful immunotherapies are monoclonal antibodies (MAbs) which target immune checkpoint inhibitor (ICI) molecules, most prominently cytotoxic T-lymphocyte-associated protein (CTLA-4) and programmed cell death protein-1 (PD-1) and its major ligand, PD-L1. These immunotherapeutic agents are, however, often associated with the occurrence of immune-mediated toxicities known as immune-related adverse events (IRAEs). The incidence of severe toxicities increases substantially when these agents are used together, particularly with CTLA-4 in combination with PD-1 or PD-L1 antagonists. Accordingly, dissociating the beneficial anti-tumor therapeutic activity of these agents from the emergence of IRAEs represents a significant challenge to attaining the optimum efficacy of ICI-targeted immunotherapy of cancer. This situation is compounded by an increasing awareness, possibly unsurprising, that both the beneficial and harmful effects of ICI-targeted therapies appear to result from an over-reactive immune system. Nevertheless, this challenge may not be insurmountable. This contention is based on acquisition of recent insights into the role of the gut microbiome and its products as determinants of the efficacy of ICI-targeted immunotherapy, as well as an increasing realization of the enigmatic involvement of Th17 cells in both anti-tumor activity and the pathogenesis of some types of IRAEs. Evidence linking the beneficial and harmful activities of ICI-targeted immunotherapy, recent mechanistic insights focusing on the gut microbiome and Th17 cells, as well as strategies to attenuate IRAEs in the setting of retention of therapeutic activity, therefore represent the major thrusts of this review.
| S-EPMC6775220 | biostudies-literature
Project description:IntroductionThe wide application of immune checkpoint inhibitors has significantly improved the survival expectation of cancer patients. While immunotherapy brings benefits to patients, it also results in a series of immune-related adverse events (irAEs). Increasing evidence suggests that the gut microbiome is critical for immunotherapy response and the development of irAEs.MethodsIn this prospective study, we recruited 95 patients with advanced/unresectable gastrointestinal cancers treated with immunotherapy and report a comprehensive analysis of the association of the gut microbiome with irAEs. Metagenome sequencing was used to analyze the differences in bacterial composition and metabolic pathways of baseline fecal samples.ResultsIn summary, we identified bacterial species and metabolic pathways that might be associated with the occurrence of irAEs in gastric, esophageal, and colon cancers. Ruminococcus callidus and Bacteroides xylanisolvens were enriched in patients without severe irAEs. Several microbial metabolic pathways involved in the urea cycle, including citrulline and arginine biosynthesis, were associated with irAEs. We also found that irAEs in different cancer types and toxicity in specific organs and the endocrine system were associated with different gut microbiota profiles. These findings provide the basis for future mechanistic exploration.
| S-EPMC10084768 | biostudies-literature
Project description:BackgroundUp to 40% of cancer patients on immune checkpoint inhibitors develop clinically significant immune-related adverse events (irAEs). The role of host immune status and function in predisposing patients to the development of irAEs remains unknown.MethodsSera from 65 patients receiving immune checkpoint inhibitors and 13 healthy controls were evaluated for 40 cytokines at pre-treatment, after 2-3 weeks and after 6 weeks and analysed for correlation with the development of irAEs.ResultsOf the 65 cancer patients enrolled, 55% were women; the mean age was 65 years and 98% received anti-PD1/PDL1 therapy. irAEs occurred in 35% of cases. Among healthy controls, cytokine levels were stable over time and lower than those in cancer patients at baseline. Significant increases in CXCL9, CXCL10, CXCL11 and CXCL13 occurred 2 weeks post treatment, and in CXCL9, CXCL10, CXCL11, CXCL13, IL-10 and CCL26 at 6 weeks post treatment. Patients who developed irAEs had lower levels of CXCL9, CXCL10, CXCL11 and CXCL19 at baseline and exhibited greater increases in CXCL9 and CXCL10 levels at post treatment compared to patients without irAEs.ConclusionsPatients who developed irAEs have lower baseline levels and greater post-treatment increases in multiple cytokine levels, suggesting that underlying immune dysregulation may be associated with heightened risk for irAEs.
| S-EPMC6325132 | biostudies-literature
Project description:The enthusiasm for immune checkpoint inhibitors (ICIs), an efficient tumor treatment model different from traditional treatment, is based on their unprecedented antitumor effect, but the occurrence of immune-related adverse events (irAEs) is an obstacle to the prospect of ICI treatment. IrAEs are a discrete toxicity caused by the nonspecific activation of the immune system and can affect almost all tissues and organs. Currently, research on biomarkers mainly focuses on the gastrointestinal tract, endocrine system, skin and lung. Several potential hypotheses concentrate on the overactivation of the immune system, excessive release of inflammatory cytokines, elevated levels of pre-existing autoantibodies, and presence of common antigens between tumors and normal tissues. This review lists the current biomarkers that might predict irAEs and their possible mechanisms for both nonspecific and organ-specific biomarkers. However, the prediction of irAEs remains a major clinical challenge to screen and identify patients who are susceptible to irAEs and likely to benefit from ICIs.
| S-EPMC7734811 | biostudies-literature
Project description:Immune checkpoint inhibitors (ICIs), which target the programmed cell death receptor-1 and cytotoxic T lymphocyte-associated antigen-4 signaling pathways, represent remarkable breakthroughs in cancer treatment and have improved survival among patients with a variety of malignancies. However, the wide use of ICIs is associated with a spectrum of immune-related adverse events (irAEs) that can affect any organ system, and may sometimes be life threatening. Rheumatic irAEs are not an infrequent type of irAE. In this systematic review, we consider the clinical characteristics of rheumatic irAEs, including patients with pre-existing rheumatic diseases, and focus on the management of rheumatic irAEs.
| S-EPMC6938753 | biostudies-literature
Project description:BackgroundSide effects of immune checkpoint inhibitors (ICIs), called immune-related adverse events (irAEs), closely resemble primary autoimmune or rheumatic diseases. We aimed to understand the clinical utility of rheumatic autoantibodies (rhAbs) for diagnosing irAEs.Patients and methodsPatients without pre-existing autoimmune disease (pAID) who had cancer treated with ICI(s) treatment from 1/1/2011 to 12/21/2020 and a rhAb checked were retrospectively identified. Logistic regression assessed associations between autoantibodies and irAEs, cancer outcome, and survival. Specificity, sensitivity, and positive/negative predictive values (PPV, NPV) were estimated for key rhAbs and ICI-arthritis. Kaplan-Meier analyzed objective response rate (ORR) and overall survival (OS).ResultsA total of 2662 patients were treated with≥1 ICIs. One hundred and thirty-five without pAID had ≥ 1 rhAb tested. Of which 70/135(52%) were female; median age at cancer diagnosis was 62 years with most common cancers: melanoma (23%) or non-small cell lung cancer (21%), 96/135 (75%) were anti-PD1/PDL1 treated. Eighty had a rhAb ordered before ICI, 96 after ICI, and 12 before and after. Eighty-two (61%) experienced an irAE, 33 (24%) with rheumatic-irAE. Pre-ICI RF showed significant association with rheumatic-irAEs (OR = 25, 95% CI, 1.52-410.86, P = .024). Pre- and post-ICI RF yielded high specificity for ICI-arthritis (93% and 78%), as did pre- and post-ICI CCP (100% and 91%). Pre-ICI RF carried 93% NPV and pre-ICI CCP had 89% PPV for ICI-arthritis. No variables were significantly correlated with ORR. Any-type irAE, rheumatic-irAE and ICI-arthritis were all associated with better OS (P = .000, P = .028, P = .019).ConclusionsPre-ICI RF was associated with higher odds of rheumatic-irAEs. IrAEs had better OS; therefore, clinical contextualization for rhAbs is critical to prevent unnecessary withholding of lifesaving ICI for fear of irAEs.
| S-EPMC10166164 | biostudies-literature