Gut microbiota and dietary intervention: affecting immunotherapy efficacy in non–small cell lung cancer
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PROVIDER: S-EPMC10867196 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Immunotherapy for non-small cell lung cancer (NSCLC) has advanced considerably over the past two decades. In particular, immune checkpoint inhibitors are widely used for treating NSCLC. However, the overall cure and survival rates of patients with NSCLC remain low. Therefore, continuous investigation into complementary treatments is necessary to expand the clinical advantages of immunotherapy to a larger cohort of patients with NSCLC. Recently, the distinctive role of the gut microbiota (GM) in the initiation, progression, and dissemination of cancer has attracted increasing attention. Emerging evidence indicates a close relationship between the gut and lungs, known as the gut-lung axis (GLA). In this review, we aim to provide a comprehensive summary of the current knowledge regarding the connection between the GM and the outcomes of immunotherapy in NSCLC, with particular focus on the recent understanding of GLA. Overall, promising GM-based therapeutic strategies have been observed to improve the effectiveness or reduce the toxicity of immunotherapy in patients with NSCLC, thus advancing the utilization of microbiota precision medicine.
| S-EPMC10701269 | biostudies-literature
Project description: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.
| S-EPMC9656313 | biostudies-literature
Project description:Cancer immunotherapy including immune checkpoint inhibitors (ICI) has revolutionized non-small cell lung cancer (NSCLC) therapy. Recently, the microbiota status "before" initiation of ICI therapy has been emphasized as a predictive biomarker in patients undergoing ICI therapy. However, the microbiota diversity and composition "during" ICI therapy is unknown. This multicenter, prospective observational study analyzed both saliva and feces from 28 patients with NSCLC. We performed 16S ribosomal RNA gene sequencing, then analyzed associations of oral and gut microbiota diversity or composition with ICI response. At the genus level, the alpha diversity of the gut microbiota was significantly greater in responders (n = 17) than in non-responders (n = 11) (Chao 1, p = 0.0174; PD whole tree, p = 0.0219; observed species, p = 0.0238; Shannon, p = 0.0362), while the beta diversity of the gut microbiota was significantly different (principal coordinates analysis, p = 0.035). Compositional differences in the gut microbiota were observed between the two groups; in particular, g_Blautia was enriched in responders, whereas o_RF32 order unclassified was enriched in non-responders. The progression-free survival (PFS) of patients enriched gut microbiota of g_Blautia was significantly longer [median survival time (MST): not reached vs. 549 days, p = 0.0480] and the PFS of patients with gut microbiota of o_RF32 unclassified was significantly shorter (MST: 49 vs. 757 days, p = 0.0205). There were no significant differences between groups in the oral microbiota. This study revealed a strong association between gut microbiota diversity and ICI response in NSCLC patients. Moreover, specific gut microbiota compositions may influence the ICI response. These findings might be useful in identifying biomarkers to predict ICI response.
| S-EPMC9638091 | biostudies-literature
Project description:IntroductionThis study was designed to identify a group of bacteria in the human gut microbiota with specific effects on PD-1-based immunotherapy for patients with non-small cell lung cancer (NSCLC).MethodsThe study was performed in patients with advanced NSCLC, who received PD-1 monoclonal antibody (mAb) treatment for 6 months after one or several prior therapies. The combination of blood immune-related factors of the participants and their 16S rRNA gene sequencing from fecal samples at baseline was used to investigate the diversity and composition of the gut microbiota. The differences in relative abundance of gut microbiota at the genus level were compared, and the relation to blood immune-related factors was assessed using Spearman's rank correlation coefficient analysis.ResultsThe 16S rRNA gene sequencing showed a clear difference in the diversity and composition of the gut microbiota between groups with stable disease (SD) and progressive disease (PD). A comparison of differences in relative abundance at the genus level showed that the relative abundance of Escherichia-Shigella, Akkermansia and Olsenella in the SD group was significantly higher than that in the PD group. The SD group had significantly higher interleukin-12 (IL-12) and interferon γ (IFN-γ) levels than the PD group. Interestingly, the numbers of white blood cells and sorted cells in the SD group were higher than those in the PD group. Spearman's rank correlation coefficient analysis showed that Escherichia-Shigella was positively correlated with IL-12, IFN-γ and basophils. Akkermansia was positively correlated with monocytes.ConclusionThe response to PD-1-based immunotherapy in patients with NSCLC is affected by the diversity and composition of the gut microbiota. Escherichia-Shigella and Akkermansia may have specific effects on PD-1 inhibitory immunotherapy for NSCLC.
| S-EPMC8593091 | biostudies-literature
Project description:BackgroundThe effects of gut microbiota and metabolites on the responses to immune checkpoint inhibitors (ICIs) in advanced epidermal growth factor receptor (EGFR) wild-type non-small cell lung cancer (NSCLC) have been studied. However, their effects on EGFR-mutated (EGFR +) NSCLC remain unknown.MethodsWe prospectively recorded the clinicopathological characteristics of patients with advanced EGFR + NSCLC and assessed potential associations between the use of antibiotics or probiotics and immunotherapy efficacy. Fecal samples were collected at baseline, early on-treatment, response and progression status and were subjected to metagenomic next-generation sequencing and ultra-high-performance liquid chromatography-mass spectrometry analyses to assess the effects of gut microbiota and metabolites on immunotherapy efficacy.ResultsThe clinical data of 74 advanced EGFR + NSCLC patients were complete and 18 patients' fecal samples were dynamically collected. Patients that used antibiotics had shorter progression-free survival (PFS) (mPFS, 4.8 vs. 6.7 months; P = 0.037); probiotics had no impact on PFS. Two dynamic types of gut microbiota during immunotherapy were identified: one type showed the lowest relative abundance at the response time point, whereas the other type showed the highest abundance at the response time point. Metabolomics revealed significant differences in metabolites distribution between responders and non-responders. Deoxycholic acid, glycerol, and quinolinic acid were enriched in responders, whereas L-citrulline was enriched in non-responders. There was a significant correlation between gut microbiota and metabolites.ConclusionsThe use of antibiotics weakens immunotherapy efficacy in patients with advanced EGFR + NSCLC. The distribution characteristics and dynamic changes of gut microbiota and metabolites may indicate the efficacy of immunotherapy in advanced EGFR + NSCLC.
| S-EPMC10985957 | biostudies-literature
Project description:BackgroundThe gut microbiota and its associated metabolites play a critical role in shaping the systemic immune response and influencing the efficacy of immunotherapy. In this study, patients with extensive-stage small cell lung cancer (ES-SCLC) were included to explore the correlation between gut microbiota and metabolites and immunotherapy efficacy in patients with ES-SCLC.MethodsPre- and post-treatment, we collected stool samples from 49 ES-SCLC patients treated with an anti-programmed death-ligand 1 (PD-L1) antibody. We then applied 16S ribosomal RNA (rRNA) sequencing and liquid chromatography-mass spectrometry (LC-MS) non-targeted metabolomics technology. Subsequently, the gut microbiota and metabolites were identified and classified.ResultsThe results showed no statistical difference in gut microbiota alpha and beta diversity between the responder (R) and non-responder (NR) patients at baseline. However, the alpha diversity of the R patients was significantly higher than that of the NR patients after treatment. There were also differences in the microbiome composition at the baseline and post-treatment. Notably, after treatment, Faecalibacterium, Clostridium_sensu_stricto_1, and [Ruminococcus]_torques were enriched in the R group, while Dubosiella, coriobacteriaceae_UCG-002 was enriched in the NR group. The non-targeted metabolomics results also indicated that short-chain fatty acids (SCFAs) were up-regulated in the R group after treatment. More, differential metabolites were enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including the PD-L1 expression and programmed death 1 (PD-1) checkpoint pathway in cancer.ConclusionsThese findings are anticipated to provide novel markers for predicting the efficacy of immune checkpoint inhibitors (ICIs) in patients with ES-SCLC, and offer new directions for further research on molecular mechanisms.
| S-EPMC11565349 | biostudies-literature
Project description:Lung cancer is one of the deadliest and most common malignancies in the world, representing one of the greatest challenges in cancer treatment. Immunotherapy is rapidly changing standard treatment schedule and outcomes for patients with advanced malignancies. However, several ongoing studies are still attempting to elucidate the biomarkers that could predict treatment response as well as the new strategies to improve antitumor immune system response ameliorating immunotherapy efficacy. The complex of bacteria, fungi, and other microorganisms, termed microbiota, that live on the epithelial barriers of the host, are involved in the initiation, progression, and dissemination of cancer. The functional role of microbiota has attracted an accumulating attention recently. Indeed, it has been demonstrated that commensal microorganisms are required for the maturation, education, and function of the immune system regulating the efficacy of immunotherapy in the anticancer response. In this review, we discuss some of the major findings depicting bacteria as crucial gatekeeper for the immune response against tumor and their role as driver of immunotherapy efficacy in lung cancer with a special focus on the distinctive role of gut and lung microbiota in the efficacy of immunotherapy treatment.
| S-EPMC6885300 | biostudies-literature
Project description:For advanced metastatic non-small-lung cancer, the landscape of actionable driver alterations is rapidly growing, with nine targetable oncogenes and seven approvals within the last 5 years. This accelerated drug development has expanded the reach of targeted therapies, and it may soon be that a majority of patients with lung adenocarcinoma will be eligible for a targeted therapy during their treatment course. With these emerging therapeutic options, it is important to understand the existing data on immune checkpoint inhibitors (ICIs), along with their efficacy and safety for each oncogene-driven lung cancer, to best guide the selection and sequencing of various therapeutic options. This article reviews the clinical data on ICIs for each of the driver oncogene defined lung cancer subtypes, including efficacy, both for ICI as monotherapy or in combination with chemotherapy or radiation; toxicities from ICI/targeted therapy in combination or in sequence; and potential strategies to enhance ICI efficacy in oncogene-driven non-small-cell lung cancers.
| S-EPMC10026098 | biostudies-literature
Project description:BackgroundImmunotherapy has made significant progress in cancer treatment; however, the responsiveness to immunotherapy varies widely among patients. Growing evidence has demonstrated the role of the gut microbiota in the efficacy of immunotherapy.Main bodyHerein, we summarise the changes in the microbiota in different cancers under various immunotherapies. The microbial-host signal transmission on immunotherapeutic responses and mechanisms associated with microbial translocation to tumours in the context of immunotherapy are also discussed. In addition, we have highlighted the clinical application value of methods for regulating the microbiota. Finally, we elaborate on the relationship between the microbiota, host and immunotherapy, and provide potential directions for future research.ConclusionDifferent microbiota cause changes in the tumour microenvironment through microbial signals thereby affecting immunotherapy efficacy. Translocation of gut microbiota and the role of extraintestinal microbiota in immunotherapy deserve attention. Microbiota regulation is a novel strategy for combination therapy with immunotherapy. Although there are several aspects that deserve further refinement and exploration with regard to administration and clinical translation. Nevertheless, it is foreseeable that the microbiota will become an integral part of cancer treatment.
| S-EPMC10713876 | biostudies-literature
Project description:Cancer cachexia exerts a negative clinical influence on patients with advanced non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI). The prognostic impact of body weight change during ICI treatment remains unknown. The gut microbiota (GM) is a key contributor to the response to ICI therapy in cancer patients. However, the association between cancer cachexia and GM and their association with the response to ICIs remains unexplored. This study examined the association of cancer cachexia with GM composition and assessed the impact of GM on clinical outcomes in patients with NSCLC treated with ICIs. In this observational, prospective study, which included 113 Japanese patients with advanced NSCLC treated with ICIs, the prevalence of cachexia was 50.4% (57/113). The median progression-free survival (PFS) and overall survival (OS) were significantly shorter in the cachexia group than in the non-cachexia group (4.3 vs. 11.6 months (p = 0.003) and 12.0 months vs. not reached (p = 0.02), respectively). A multivariable analysis revealed that baseline cachexia was independently associated with a shorter PFS. Moreover, a gain in body weight from the baseline (reversible cachexia) was associated with a significantly longer PFS and OS compared to irreversible cachexia. Microbiome profiling with 16S rRNA analysis revealed that the cachexia group presented an overrepresentation of the commensal bacteria, Escherichia-Shigella and Hungatella, while the non-cachexia group had a preponderance of Anaerostipes, Blautia, and Eubacterium ventriosum. Anaerostipes and E. ventriosum were associated with longer PFS and OS. Moreover, a cachexia status correlated with the systemic inflammatory marker-derived-neutrophil-to-lymphocytes ratio (dNLR) and Lung Immune Prognostic Index (LIPI) indexes. Our study demonstrates that cachexia and longitudinal bodyweight change have a prognostic impact on patients with advanced NSCLC treated with ICI therapy. Moreover, our study demonstrates that bacteria associated with ICI resistance are also linked to cachexia. Targeted microbiota interventions may represent a new type of treatment to overcome cachexia in patients with NSCLC.
| S-EPMC9658074 | biostudies-literature