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Cited by 550Gut microbiota and healthCancer Immunotherapy and BiomarkersHepatocellular Carcinoma Treatment and Prognosis

Gut microbiome affects the response to anti-PD-1 immunotherapy in patients with hepatocellular carcinoma

Open access
Zheng, Yi, Wang, Tingting, Tu, Xiaoxuan, Huang, Yun, Zhang, Hangyu, Tan, Di, Jiang, Weiqin, Cai, Shunfeng +5 more·2019·Journal for ImmunoTherapy of Cancer
DOI 10.1186/s40425-019-0650-9PMC PMC6651993
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Abstract

BACKGROUND: Checkpoint-blockade immunotherapy targeting programmed cell death protein 1 (PD-1) has recently shown promising efficacy in hepatocellular carcinoma (HCC). However, the factors affecting and predicting the response to anti-PD-1 immunotherapy in HCC are still unclear. Herein, we report the dynamic variation characteristics and specificities of the gut microbiome during anti-PD-1 immunotherapy in HCC using metagenomic sequencing. RESULTS: Fecal samples from patients responding to immunotherapy showed higher taxa richness and more gene counts than those of non-responders. For dynamic analysis during anti-PD-1 immunotherapy, the dissimilarity of beta diversity became prominent across patients as early as Week 6. In non-responders, Proteobacteria increased from Week 3, and became predominant at Week 12. Twenty responder-enriched species, including Akkermansia muciniphila and Ruminococcaceae spp., were further identified. The related functional genes and metabolic pathway analysis, such as carbohydrate metabolism and methanogenesis, verified the potential bioactivities of responder-enriched species. CONCLUSIONS: Gut microbiome may have a critical impact on the responses of HCC patients treated with anti-PD-1 immunotherapy. The dynamic variation characteristics of the gut microbiome may provide early predictions of the outcomes of immunotherapy in HCC, which is critical for disease-monitoring and treatment decision-making.

AI snapshot

Written from the paper’s full text.

TL;DR

In eight HCC patients treated with anti-PD-1 camrelizumab, fecal metagenomics showed responders had higher taxa richness and gene counts and distinct microbiome trajectories, with Proteobacteria increasing early in non-responders. Twenty responder-enriched species, including *Akkermansia muciniphila* and Ruminococcaceae spp., were identified, but causality remains unknown.

Key findings

  • Among 8 BCLC Stage C HCC patients (responders n = 3; non-responders n = 5), responders showed higher taxa richness and more gene counts than non-responders over the entire treatment.
  • Beta diversity inter-group dissimilarity became significantly higher than intra-group differentiation as early as Week 6; in non-responders, Proteobacteria increased from Week 3 and became predominant at Week 12, mainly due to *Escherichia coli*, while responders remained relatively stable at the phylum level.
  • LEfSe identified 20 responder-enriched and 15 non-responder-enriched species; responder-enriched species included *Akkermansia muciniphila*, Ruminococcaceae spp., Lachnospiraceae bacterium 7_1_58FAA, four *Lactobacillus* species, *Bifidobacterium dentium*, and *Streptococcus thermophilus*.
  • A total of 189 KEGG orthologies were enriched in responders, and 123 responder-enriched KOs positively correlated with 18 responder-enriched species; associated pathways included carbohydrate metabolism, methanogenesis, sulfate reduction, carbon fixation, carotenoid biosynthesis, and unsaturated fatty acid metabolism.

Methods

  • Single-center cohort of 8 histologically confirmed HCC patients with BCLC Stage C disease progressing on sorafenib; patients received camrelizumab (SHR-1210) at 3 mg/kg intravenously every 3 weeks, with response assessed every 6 weeks by RECIST 1.1. Responders were complete/partial response or stable disease ≥6 months; non-responders were progressed disease or stable disease <6 months.
  • Fresh fecal samples were collected at baseline, Week 1, and every 3 weeks until progression; metagenomic sequencing generated 49 datasets (28 from responders, 21 from non-responders). Taxonomic profiling used MetaPhlAn, and gene annotation used the integrated gene catalog and KEGG.
  • Analyses included Wilcoxon rank-sum tests, Bray-Curtis dissimilarity/PCoA, LEfSe (LDA score cutoff 2.0, P < 0.05), SparCC correlation networks, and Spearman correlations (rho > 0.5; P < 0.01 for species-KO networks).

Limitations

  • The authors state that the study highlights correlative associations and that any causal relationship remains unknown; they call for future meta-omic strategies and mouse fecal microbiota transplantation models to validate mechanisms.
  • Evident from the text: the sample is very small (8 patients; 3 responders, 5 non-responders), from one hospital, with unequal observation durations (39, 21, and 18 weeks for responders; 6, 6, 9, 9, and 12 weeks for non-responders), limiting generalizability and statistical power.
  • The authors note that future longitudinal studies should include both fecal and oral microbiome samples for a more comprehensive view.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1186/s40425-019-0650-9

Cites

25 of 25 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 17 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Fifteen non-responder-enriched species were identified.

    “Twenty R-enriched species and fifteen NR-enriched species were identified”
    Quote in the paperNot a substantial claim
  • Findingown data

    Bacteroidetes were the most abundant phylum, followed by Firmicutes and Proteobacteria, in the fecal microbiome of both responders and non-responders before treatment.

    “Specifically, Bacteroidetes were most abundant, followed by Firmicutes and Proteobacteria.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Twenty responder-enriched species were identified, including Akkermansia muciniphila and Ruminococcaceae spp.

    “Twenty responder-enriched species, including Akkermansia muciniphila and Ruminococcaceae spp., were further identified.”
    • Also stated in: § Results and discussion · plain
      “Twenty R-enriched species and fifteen NR-enriched species were identified”
    Quote in the paperSubstantial claim
  • Findingown data

    Among R-enriched bacteria, the four Lactobacillus species were most significantly correlated with each other.

    “Among the R-enriched bacteria, the four Lactobacillus species were most significantly correlated with each other”
    Quote in the paperNot a substantial claim
  • Findingown data

    Microbial composition at the phylum level in responders remained relatively stable during treatment.

    “As treatment proceeded, microbial composition at the phylum level in R remained relatively stable.”
    Quote in the paperSubstantial claim
  • May combine two claims. 12
  • Classified as probably not a substantial claim. 16

  • May combine two claims.

    Findingown data

    Fecal samples from HCC patients responding to anti-PD-1 immunotherapy showed higher taxa richness and more gene counts than those of non-responders.

    “Fecal samples from patients responding to immunotherapy showed higher taxa richness and more gene counts than those of non-responders.”
    • Also stated in: § Results and discussion · plain
      “Over the entire treatment, R showed higher taxa richness and more gene counts than those of NR (Fig. 1a).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The number of significant positive-correlation pairs and the correlation strengths in R-enriched species were higher than those of NR-enriched species.

    “The number of significant positive-correlation pairs and the correlation strengths in R-enriched species were higher than those of NR-enriched species.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Other pathways with potential benefits included sulfate reduction (ko00920) and carbon fixation (ko00720) correlated with R. obeum, carotenoid biosynthesis (ko00906) correlated with B. cellulosilyticus and A. colihominis, and unsaturated fatty acid metabolism (ko00590) associated with C. comes.

    “Other pathways with potential benefits included sulfate reduction (ko00920) and carbon fixation (ko00720) functions that were correlated with R. obeum, carotenoid biosynthesis (ko00906) correlated with B. cellulosilyticus and A. colihominis, and unsaturated fatty acid metabolism (ko00590) associated with C. comes”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In non-responders, Proteobacteria increased from Week 3 and became predominant at Week 12.

    “In non-responders, Proteobacteria increased from Week 3, and became predominant at Week 12.”
    • Also stated in: § Results and discussion · plain
      “in NR, Proteobacteria markedly increased as early as Week 3, and became predominant at Week 12”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The present study showed different trajectories of microbiome shifts between responders and non-responders and revealed a stronger stability of the gut microbiome in responders during the whole course of treatment.

    “the present study showed the different trajectories of microbiome shifts between R and NR and revealed a stronger stability of the gut microbiome in R during the whole course of treatment.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Factors including age, genetics, and diet may influence microbiome composition.

    “It is well recognized that factors including age, genetics, and diet may influence microbiome composition [14].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334(6052):105–8. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The findings indicate biological significance of particular bacterial strains during anti-PD-1 immunotherapy in HCC and may provide support for development of a gut-microbiome-modulation scheme in immunotherapy.

    “Our findings further indicated the biological significance of particular bacterial strains during anti-PD-1 immunotherapy in HCC and may provide support for the development of a gut-microbiome-modulation scheme in immunotherapy.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    An individual's microbiota could be remarkably stable, with 60% of strains remaining over the course of five years.

    “A study demonstrated that an individual’s microbiota could be remarkably stable, with 60% of strains remaining over the course of five years”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Faith JJ, Guruge JL, Charbonneau M, Subramanian S, Seedorf H, Goodman AL, et al. The long-term stability of the human gut microbiota. Science. 2013;341(6141):1237439. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Gopalakrishnan et al. found a statistically significant positive correlation between CD8+ T cell infiltrate in the tumor and the Faecalibacterium genus as well as the Ruminococcaceae family.

    “Gopalakrishnan et al. compared the tumor-associated immune infiltrates via multi-parameter immunohistochemistry (IHC) and found a statistically significant positive correlation between CD8+ T cell infiltrate in the tumor and the Faecalibacterium genus as well as the Ruminococcaceae family”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7] Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359(6371):97–103. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Both cellulose and pectin have been highlighted for their prebiotic and anti-inflammatory potential as dietary fibers.

    “Both cellulose and pectin have been highlighted for their prebiotic and anti-inflammatory potential as dietary fibers [11, 12].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [11] Shoaie S, Ghaffari P, Kovatcheva-Datchary P, Mardinoglu A, Sen P, Pujos-Guillot E, et al. Quantifying diet-induced metabolic changes of the Human gut Microbiome. Cell Metab. 2015;22(2):320–31. source

      Not checked in the free run.

    • cites [12] Chung WSF, Meijerink M, Zeuner B, Holck J, Louis P, Meyer AS, et al. Prebiotic potential of pectin and pectic oligosaccharides to promote anti-inflammatory commensal bacteria in the human colon. FEMS Microbiol Ecol. 2017;1, 93(11). source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In previous studies, a significantly higher relative abundance of Ruminococcaceae was identified in melanoma patients responding to anti-PD-1 immunotherapy.

    “In previous studies, a significantly higher relative abundance of Ruminococcaceae was identified in melanoma patients responding to anti-PD-1 immunotherapy [7]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7] Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359(6371):97–103. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Any causal relationship of the correlative associations between changes in the gut microbiome and host-immune responses to drugs remains unknown.

    “Although our present microbiome-wide association study highlighted the association between changes in the gut microbiome and host-immune responses to drugs, any causal relationship of these correlative associations remains unknown.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Oral administration of Bifidobacterium could improve tumor control efficacy of PD-L1-specific antibody therapy.

    “Oral administration of Bifidobacterium could improve tumor control efficacy of programmed cell death protein 1 ligand 1 (PD-L1)-specific antibody therapy [10]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015;350(6264):1084–9. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Oral supplementation with A. muciniphila could restore the efficacy of anti-PD-1 immunotherapy.

    “oral supplementation with A. muciniphila could restore the efficacy of anti-PD-1 immunotherapy [8]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [8] Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillere R, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018;359(6371):91–7. source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductreasoning

    In the present study, patients were enrolled with strict criteria to minimize potential dietary or geographical influences during the whole course of treatment, and to ensure that dynamic changes of gut microbiota in both R and NR were attributed to the therapeutic intervention instead of daily factors.

    “In the present study, patients were enrolled with strict criteria to minimize potential dietary or geographical influences during the whole course of treatment, as well as to ensure that the dynamic changes of gut microbiota in both R and NR were attributed to the therapeutic intervention instead of any daily factors.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Methane generated in the human gastrointestinal tract has been reported to ameliorate oxidative stress injury and suppress the host inflammatory response.

    “Methane generated in human gastrointestinal tract has been reported to ameliorate oxidative stress injury and suppress the host inflammatory response [13].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Zhang X, Li N, Shao H, Meng Y, Wang L, Wu Q, et al. Methane limit LPS-induced NF-kappaB/MAPKs signal in macrophages and suppress immune response in mice by enhancing PI3K/AKT/GSK-3beta-mediated IL-10 expression. Sci Rep. 2016;6:29359. source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductreasoning

    Samples were collected only from one hospital with local individuals who shared common dietary intake patterns.

    “we collected samples only from one hospital with local individuals who shared common dietary intake patterns.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    78.12% of the raw reads were high-quality, with an average length of 72 bp and an average Q35 score of 100%.

    “Overall, 78.12% of the raw reads were regarded as high-quality reads, with an average length of 72 bp and an average Q35 score of 100% (Additional file 8: Table S3).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In two multicenter phase 2 studies, the objective response rate of anti-PD-1 immunotherapy in sorafenib-refractory HCC was nearly 20%, quadrupling that of sorafenib.

    “In two multicenter, phase 2 studies [3, 4] investigating the efficacy of anti-PD-1 immunotherapy in sorafenib-refractory HCC, the ORR was nearly 20%, which quadrupled that of sorafenib.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [3] El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet (London, England). 2017;389(10088):2492–502. source

      Not checked in the free run.

    • cites [4] Zhu AX, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmer D, et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. The Lancet Oncology. 2018;19(7):940–52. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    No antibiotics were applied during treatment.

    “During the treatment, no antibiotics were applied.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    None of the patients had experienced diarrhea or other intestinal symptoms, or antibiotic/probiotic consumption during the study.

    “None of the patients had experienced diarrhea or other intestinal symptoms, or antibiotic/probiotic consumption during the study.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Patients were asked to keep their own dietary and other habits during drug treatment to avoid any interruption to their inherent gut microbiome.

    “Patients were asked to keep their own dietary and other habits during drug treatment to avoid any interruption to their inherent gut microbiome.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The role of the gut microbiome in modulating tumor responses to immunotherapy in melanoma, non-small cell lung cancer, renal cell carcinoma, and urothelial carcinoma has received increased attention across a series of studies.

    “The role of the gut microbiome in modulating tumor responses to immunotherapy in melanoma [5–7], non-small cell lung cancer, renal cell carcinoma, and urothelial carcinoma [6, 8] has received increased attention across a series of studies in recent years.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [5] Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, Alegre ML, et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science. 2018;359(6371):104. source

      Not checked in the free run.

    • cites [6] Vetizou M, Pitt JM, Daillere R, Lepage P, Waldschmitt N, Flament C, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015;350(6264):1079–84. source

      Not checked in the free run.

    • cites [7] Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359(6371):97–103. source

      Not checked in the free run.

    • cites [8] Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillere R, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018;359(6371):91–7. source

      Not checked in the free run.

23 of 23

  • The paper relies on this without support.

    Factors affecting and predicting the response to anti-PD-1 immunotherapy in HCC are still unclear.

    “However, the factors affecting and predicting the response to anti-PD-1 immunotherapy in HCC are still unclear.”

  • The paper relies on this without support.

    Data concerning the impact of the gut microbiome on HCC immunotherapy have not been reported.

    “However, data concerning the impact of the gut microbiome on HCC immunotherapy have not been reported.”

  • The paper relies on this without support.

    Previous research has focused more on the baseline status rather than a dynamic variation of the gut microbiome during immunotherapy.

    “Additionally, previous research to date has tended to focus more on the baseline status rather than a dynamic variation of the gut microbiome during immunotherapy.”

  • The paper relies on this without support.

    This is the first study to focus on the association between the gut microbiome and the response to anti-PD-1 immunotherapy for HCC.

    “To our knowledge, this is the first study to focus on the association between the gut microbiome and the response to anti-PD-1 immunotherapy for HCC.”

  • The paper relies on this without support.

    Commensal A. muciniphila and Ruminococcaceae benefited host health by preventing increases in intestinal permeability and systemic immunosuppression.

    “Commensal A.muciniphila and Ruminococcaceae benefited host health by preventing increases in intestinal permeability and systemic immunosuppression.”

  • The paper relies on this without support.

    Four Lactobacillus species (L. oris, L. mucosae, L. gasseri, L. vaginalis), Bifidobacterium dentium, and Streptococcus thermophilus were probiotic lactic acid bacteria beneficial to host metabolism and immunity by inhibiting the growth of pathogenic microorganisms.

    “Among the R-enriched species, four Lactobacillus species (L. oris, L. mucosae, L. gasseri, and L. vaginalis), Bifidobacterium dentium and Streptococcus thermophilus were probiotic lactic acid bacteria, which were beneficial to host metabolism and immunity by inhibiting the growth of pathogenic microorganisms and accompanying spoilage agents.”

  • The paper relies on this without support.

    Coprococcus comes, Bacteroides cellulosilyticus, and Subdoligranulum sp. possessed probiotic potential related with dietary fiber digestion and short-chain fatty acid production.

    “Coprococcus comes, Bacteroides cellulosilyticus, and Subdoligranulum sp. also possessed probiotic potential, as they were reported to be related with dietary fiber digestion and short-chain fatty acid production.”
7 of 7

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Zheng et al. reported dynamic alterations within gut microbiome in patients with HCC during their immunotherapy, and metagenomic sequencing data showed higher taxa in faecal samples of patients responding to immunotherapy compared to non-responders.

    “In recently published work, Zheng et al. reported some dynamic alterations within gut microbiome in patients with HCC during their immunotherapy. Moreover, metagenomic sequencing data showed higher taxa in faecal samples of patients, responding to immunotherapy compared to non-responders, highlighting the role of microbiome in regulating immune responses [123].”

    From Immune Checkpoint Inhibitors in Cancer Therapy (2022) · cites this paper as [123]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Responder definition differs at the six-month boundary

    Minor

    The Results define responders with stable disease lasting over six months, while the Methods include stable disease lasting for at least six months. These definitions classify a patient with exactly six months of stable disease differently.

  • Species-correlation network has conflicting methods and thresholds

    Minor

    The Fig. 2 caption describes the species-correlation network as Spearman correlations with P < 0.01. The Methods instead say species correlations were calculated with SparCC and displayed at P < 0.05; they reserve Spearman correlations for bacteria-KO associations.

2 of 2

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Authors
Zheng, Y., Wang, T., Tu, X., Huang, Y., Zhang, H., Tan, D., Jiang, W., Cai, S., Zhao, P., Song, R., Li, P., Qin, N., & Fang, W.
Affiliations
  • First Affiliated Hospital Zhejiang University (CN)
  • Tongji University (CN)
Corresponding author
  • Qin, Nan
  • Fang, Weijia
ORCID
Venue
Journal for ImmunoTherapy of Cancer
Publisher
BMJ
Published
2019-07-23
Volume
7
Issue
1
Pages
193-193
ISSN
2051-1426 (ISSN-L)
DOI
10.1186/s40425-019-0650-9
PMC
PMC6651993
OpenAlex
W2963245811
Semantic Scholar
b606fc8639924cb49453655568254e8fdcafad57
Cited by
550
References
25
Citations by year
2026: 68 · 2025: 84 · 2024: 86 · 2023: 99 · 2022: 87 · 2021: 72 · 2020: 47 · 2019: 6 · 2013: 1
FWCI
17.54
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal for ImmunoTherapy of Cancer (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (31670118)
  • the Key Subject of Clinical Medical Engineering of Zhejiang Province (No. G3221)
  • Natural Science Foundation of Zhejiang Province (LR15H030002)
  • the Major Scientific Project of Zhejiang Province (2017C03028)
  • S&T Major Project of China (2017ZX10203205)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
Keywords
gut microbiota, anti-PD-1 therapy, hepatocellular carcinoma, immunotherapy response prediction, Akkermansia muciniphila, Ruminococcaceae, Proteobacteria, beta diversity, methanogenesis, carbohydrate metabolism, metagenomics
MeSH terms
Clinical Decision-Making, Gastrointestinal Microbiome, Bacteria, Carcinoma, Hepatocellular, Humans, Immunotherapy, Liver Neoplasms, Phylogeny, Treatment Outcome, Sequence Analysis, DNA, Metabolic Networks and Pathways, Metagenomics, Programmed Cell Death 1 Receptor, Antibodies, Monoclonal, Humanized

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