Role of the Microbiome and Diet for Response to Cancer Checkpoint Immunotherapy: A Narrative Review of Clinical Trials

Current Oncology Reports, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

The advent of checkpoint immunotherapy has dramatically changed the outcomes for patients with cancer. However, a considerable number have little or no response to therapy. We review recent findings on connection between gut microbiota and immune system, exploring whether this link could enhance effectiveness immunotherapy. Clinical studies reported specific types bacteria in larger quantities at baseline responders than non-responders, especially Akkermansia mucinifila, Ruminococcaceae, Faecalibacterium, Lachnospiraceae. Following consumption high-fiber diet, ferment dietary fiber short-chain fatty acids (SCFAs), like acetate, propionate, butyrate. Some SCFAs nurture intestinal epithelial cells, some enter bloodstream. Here can activate DC8 + cytotoxic T-cells induce cancer cell death. High intake diet was associated reduced risk progression death during Recent demonstrate that plant-based diets such as Mediterranean Diet positively influence whereas antibiotics proton pump inhibitors negatively by changing microbiota. This narrative provides evidence an association their metabolites favorable responses Prospective clinical trials are needed determine if interventions improve treatment outcomes.

Language: Английский

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Exploring the Role of the Gut Microbiota in Modulating Colorectal Cancer Immunity

Cells, Journal Year: 2024, Volume and Issue: 13(17), P. 1437 - 1437

Published: Aug. 27, 2024

The gut microbiota plays an essential role in maintaining immune homeostasis and influencing the landscape within tumor microenvironment. This review aims to elucidate interactions between dynamics, with a focus on colorectal cancer (CRC). spans foundational concepts of immuno-microbial interplay, factors microbiome composition, evidence linking immunotherapy outcomes. Gut modulates anti-cancer immunity through several mechanisms, including enhancement surveillance modulation inflammatory responses. Specific microbial species their metabolic byproducts can significantly influence efficacy immunotherapies. Furthermore, diversity correlates clinical outcomes CRC, suggesting potential as valuable biomarker for predicting response immunotherapy. Conclusions: Understanding relationship responses offers novel therapeutic strategies development. not only influences natural history treatment CRC but also serves critical modulator activity. Further exploration into microbiome's could enhance effectiveness existing treatments guide development new modalities.

Language: Английский

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The correlation between LAG-3 expression and the efficacy of chemoimmunotherapy in advanced biliary tract cancer

Cancer Immunology Immunotherapy, Journal Year: 2025, Volume and Issue: 74(2)

Published: Jan. 3, 2025

Abstract In our previous phase II T1219 trial for advanced biliary tract cancer (ABTC), the combination of nivolumab with modified gemcitabine and S-1 exhibited promising efficacy, while programmed-death-ligand-1 (PD-L1) expression did not predict chemoimmunotherapy efficacy. Lymphocyte-activation-gene-3 (LAG-3), a negative immune checkpoint, is frequently co-expressed PD-L1. This study assessed predictive value LAG-3 in ABTC patients who received chemoimmunotherapy. We analyzed 44 formalin-fixed samples using immunohistochemical staining PD-L1 correlated them clinical efficacy Digital spatial profiling was conducted selected regions interest to examine cell infiltration checkpoint six cases. Three public BTC datasets were used analysis: TCGA-CHOL, GSE32225, GSE132305. positivity observed 38.6% significantly ( P < 0.001). The objective response rate (ORR) higher LAG-3-positive tumors than LAG-3-negative (70.6% vs. 33.3%, = 0.029). level associated an increased ORR (33%, 58%, 100% 1%, 1–9%, ≥ 10%, respectively; 0.018) deeper therapeutic (20.1%, 38.6%, 57.6% same respective groups; 0.04). positively numerous checkpoints. Enrichment CD8 + T cells BTC, indicating that may serve as biomarker identifying immune-inflamed predicting ABTC.

Language: Английский

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Disentangling the molecular mystery of tumour–microbiota interactions: Microbial metabolites

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(11)

Published: Nov. 1, 2024

Abstract The profound impact of the microbiota on initiation and progression cancer has been a focus attention. In recent years, many studies have shown that microbial metabolites serve as key hubs connect microbiome progression, but underlying molecular mechanisms not fully elucidated. Multiple influence tumour development therapy resistance, including disrupting cellular signalling pathways, triggering oxidative stress, inducing metabolic reprogramming reshaping immune microenvironment, are reviewed. Focusing advancements in this field, review also summarises methodological framework regarding metabolites. review, we outline current state research tumour‐associated describe challenges future scientific clinical applications. Key points Metabolites derived from both gut intratumoural play important roles progression. dual pose an obstacle for translations. Absolute quantification tracing techniques essential addressing gaps Integrating metabolomics with multi‐omics transcends paradigms.

Language: Английский

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Understanding the role of the gut microbiome in solid tumor responses to immune checkpoint inhibitors for personalized therapeutic strategies: a review

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 7, 2025

Immunotherapy, especially immune checkpoint inhibitor (ICI) therapy, has yielded remarkable outcomes for some patients with solid cancers, but others do not respond to these treatments. Recent research identified the gut microbiota as a key modulator of responses, suggesting that its composition is closely linked responses ICI therapy in cancer treatment. As result, microbiome gaining attention potential biomarker predicting individual and target enhancing treatment efficacy. In this review, we discuss findings from human observational studies assessing effect antibiotic use prior on identifying specific bacteria associated favorable unfavorable responses. Moreover, review investigating possibility patient outcome prediction using machine learning models based data before starting clinical trials exploring whether modulation, example via fecal transplantation or live biotherapeutic products, can improve results cancer. We also briefly mechanisms through which microbial-derived products influence immunotherapy effectiveness. Further necessary fully understand complex interactions between host, microbiota, develop personalized strategies optimize therapy.

Language: Английский

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Gut microbiota as a new target for anticancer therapy: from mechanism to means of regulation

npj Biofilms and Microbiomes, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 11, 2025

In order to decipher the relationship between gut microbiota imbalance and cancer, this paper reviewed role of intestinal in anticancer therapy related mechanisms, discussed current research status as a biomarker finally summarized reasonable means regulating assist cancer therapy. Overall, our study reveals that can serve potential target for improving management.

Language: Английский

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Revealing gut microbiota biomarkers associated with melanoma immunotherapy response and key bacteria-fungi interaction relationships: evidence from metagenomics, machine learning, and SHAP methodology

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 18, 2025

The gut microbiota is associated with the response to immunotherapy in cutaneous melanoma (CM). However, fungal biomarkers and bacterial-fungal interactions have yet be determined. Metagenomic sequencing data of stool samples collected before from three independent groups European ancestry CM patients were collected. After characterizing relative abundances bacteria fungi, Linear Discriminant Analysis Effect Size (LEfSe) analysis, Random Forest (RF) model construction, SHapley Additive exPlanations (SHAP) methodology applied identify key responders CM. Diversity analysis revealed significant differences bacterial composition between non-responders. LEfSe identified 45 4 taxa as potential biomarkers. constructing RF model, AUC models built using separately 0.64 0.65, respectively. when combined, merged increased 0.71. In following important biomarkers: Romboutsia, Endomicrobium, Aggregatilinea, Candidatus Moduliflexus, Colwellia, Akkermansia, Mucispirillum, Rutstroemia, which responders, whereas Zancudomyces was Moreover, positive correlation interaction Akkermansia Rutstroemia considered a response. Our results provide valuable insights for enrichment patients. this study highlights critical role immunotherapy.

Language: Английский

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Qingjie Fuzheng Granule prevents colitis-associated colorectal cancer by inhibiting abnormal activation of NOD2/NF-κB signaling pathway mediated by gut microbiota disorder

Chinese Herbal Medicines, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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Neoadjuvant cobimetinib and atezolizumab with or without vemurafenib for stage III melanoma: outcomes and the impact of the microbiome from the NeoACTIVATE trial

Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(4), P. e011706 - e011706

Published: April 1, 2025

Background Neoadjuvant treatment has become standard for patients with high-risk operable stage III melanoma, but the optimal regimen is unknown. Targeted therapy approaches yield high pathological response rates, while immunotherapy regimens show favorable recurrence-free survival (RFS). NeoACTIVATE was designed to address whether a neoadjuvant combination of both targeted and might leverage benefits each. Methods We tested 12 weeks vemurafenib, cobimetinib, atezolizumab BRAF-mutated (BRAFm) melanoma (cohort A) cobimetinib BRAF-wild-type (BRAFwt) B), which we have shown generate substantial major response. After therapeutic lymph node dissection, received 24 adjuvant atezolizumab. Here, report outcomes their association biomarkers assayed among gut microbiome peripheral blood immune subsets. Results With 49 months median follow-up, RFS not reached cohort A 40.8 B. At after operation, 2 14 4 13 B had experienced distant relapse. Key findings from correlative analyses included diversity, taxonomic functional metagenomic signals associated metastasis-free at years. Notably, observed strong correlation between low microbial arginine biosynthesis (required T-cell activation effector function) early recurrence (p=0.0005), correlated differential abundance findings. Peripheral monitoring revealed increased double-positive (CD4+CD8+) T cells in recurrence. Conclusions atezolizumab±vemurafenib rate metastasis melanoma. Freedom highly differences structure pathway alterations known modulate cell immunity. Identification predictive will permit optimization individual patients. Trial registration number NCT03554083 .

Language: Английский

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Microbiota and Cytokine Modulation: Innovations in Enhancing Anticancer Immunity and Personalized Cancer Therapies

Biomedicines, Journal Year: 2024, Volume and Issue: 12(12), P. 2776 - 2776

Published: Dec. 6, 2024

The gut microbiota plays a crucial role in modulating anticancer immunity, significantly impacting the effectiveness of various cancer therapies, including immunotherapy, chemotherapy, and radiotherapy. Its impact on development is complex; certain bacteria, like

Language: Английский

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