CoChat
Sign Up
Cited by 1,392Gut microbiota and healthCancer Immunotherapy and BiomarkersCancer Research and Treatments

The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy

Open access
Gopalakrishnan, Vancheswaran, Helmink, Beth A., Spencer, Christine N., Reuben, Alexandre, Wargo, Jennifer A.·2018·Cancer Cell
DOI 10.1016/j.ccell.2018.03.015PMC PMC6529202
Open this paper in CoChat — free accountOpen PDF

Abstract

The microbiome is receiving significant attention given its influence on a host of human diseases including cancer. Its role in response to cancer treatment is becoming increasingly apparent, with evidence suggesting that modulating the gut microbiome may impact responses to numerous forms of cancer therapy. A working knowledge of the microbiome is vital as we move forward in this age of precision medicine, and an understanding of the microbiome’s influence on immune responses and cancer is key. It is also important to understand factors influencing the gut microbiome and strategies to manipulate the microbiome to augment therapeutic responses.

Integrity signals

Registry

Crossref · 10.1016/j.ccell.2018.03.015

Cites

72 of 72 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 128 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    B and T cells primed by commensal antigen in mesenteric lymph nodes can circulate systemically and support immune responses at distant sites against the same organism or cross-reactive antigens.

    “B and T cells, including Tregs and Th17 cells can, upon being primed by DCs presenting antigen derived from commensal organisms in draining mLNs of the gut, circulate systemically to facilitate immune responses at distant sites”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Stary et al., 2015 source

      Not checked in the free run.

  • Premisecitation

    Health-promoting bacteria such as Faecalibacterium and Ruminococcus are reduced after stem cell transplant.

    “health-promoting bacteria such as Faecalibacterium and Ruminococcus were reduced”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Biagi et al., 2015 source

      Not checked in the free run.

  • Premisecitation

    There is strong evidence that the microbiota shapes the immune system overall.

    “there is compelling evidence that the microbiota helps to shape the immune system as a whole”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Honda and Littman, 2016

      Not checked in the free run.

  • Premisecitation

    Evidence is accumulating that the microbiome affects how cancer therapy works.

    “There is mounting evidence supporting the role of the microbiome in response to cancer therapy”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Chaput et al., 2017 source

      Not checked in the free run.

    • cites Gopalakrishnan et al., 2018 source

      Not checked in the free run.

    • cites Routy et al., 2018 source

      Not checked in the free run.

  • Premisecitation

    Recent studies show that the gut microbiome influences response to immune checkpoint blockade across multiple cancer types.

    “several recent studies demonstrating the influence of the gut microbiome specifically on the response to immune checkpoint blockade across cancer types”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Chaput et al., 2017 source

      Not checked in the free run.

    • cites Frankel et al., 2017 source

      Not checked in the free run.

    • cites Gopalakrishnan et al., 2018 source

      Not checked in the free run.

  • May combine two claims. 37
  • Classified as probably not a substantial claim. 6
  • The quote only partly states this claim. 1

  • May combine two claims.

    Premisecitation

    Th17 cytokine secretion stimulates intestinal epithelial cells to form tight junctions and secrete antimicrobial proteins.

    “cytokine secretion from Th17 cells stimulates IECs to form tight junctions and to secrete anti-microbial proteins”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Weaver et al., 2013 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Lower gut microbiota diversity at the time of stem cell transplant is associated with shorter overall survival and higher transplant-related mortality than higher diversity.

    “patients having a lower diversity of microbiota in their gut at the time of HSCT having shortened overall survival and higher mortality rates (specifically transplant-related mortality) compared to those with a high diversity of gut microbiota”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Taur et al., 2014 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Germ-free mice lacking intestinal microbiota have severe immune defects, including absent mucous layer, altered IgA secretion, and reduced Peyer's patches and mesenteric lymph nodes.

    “germ-free (GF) mice that lack intestinal microbiota are noted to have severe defects in immunity, with an absent mucous layer, altered IgA secretion and reduced size and functionality of Peyer’s patches and draining mesenteric lymph nodes”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Johansson et al., 2015 source

      Not checked in the free run.

    • cites Spiljar et al., 2017 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Dysbiosis can impair local, locoregional and systemic immune responses, with mucosal barrier breakdown, bacterial translocation, inflammatory cytokine changes, Th17 and effector T cell activation, and neutrophil influx.

    “Dysbiosis can lead to impaired local, locoregional, and systemic immune responses with breakdown of mucosal barriers, translocation of gut bacteria to the mLNs and into the peripheral circulation”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Levy et al., 2017 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Th17 cells are markedly depleted in germ-free animals and can be induced by specific bacterial subsets such as segmented filamentous bacteria.

    “Th17 cells are markedly depleted in GF animals and can be induced by specific bacterial subsets such as segmented filamentous bacteria (SFB)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Ivanov et al., 2009 source

      Not checked in the free run.

    • cites Ivanov et al., 2008 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SCFAs help maintain gut Tregs through histone deacetylase inhibition, suggesting epigenetic regulation.

    “SCFAs here function in a manner dependent on their ability to inhibit histone deacetylase activity suggesting epigenetic regulation”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Rooks and Garrett, 2016

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    IgA blocks bacterial adherence to epithelial cells, promotes agglutination, entrapment and clearance, and directly affects bacterial virulence.

    “IgA acts primarily by blocking bacterial adherence to epithelial cells; agglutination, entrapment and clearance; and also has direct effects on bacterial virulence”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Mantis et al., 2011 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    TLR signaling from microbial peptides to dendritic cells and innate effectors produces cytokines and interferons that act locally and distantly, creating immune system tone.

    “Toll-like receptor signaling from microbial peptides to DCs and other innate immune effectors generates cytokines and interferons that act in both a paracrine and endocrine manner at distant sites”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Abt et al., 2012 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    After allogeneic stem cell transplant, the gut microbiota loses diversity and stability and becomes dominated by Enterococcus, Streptococcus and Proteobacteria.

    “a disruption of the existing state of equilibrium of the gut microbiota post-HSCT with a relative dysbiosis and a loss of bacterial diversity and stability and dominance of Enterococcus, Streptococcus and various Proteobacteria”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Holler et al., 2014 source

      Not checked in the free run.

    • cites Taur et al., 2012 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Dysbiosis and impaired systemic immunity are common in allogeneic stem cell transplant patients because of immunosuppressants, broad-spectrum antibiotics and total body irradiation.

    “Dysbiosis and impaired systemic immunity is fairly common in these patients, as they are often treated with concurrent therapies that significantly alter immunity and composition of the gut microbiota”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Routy et al., 2017 source

      Not checked in the free run.

    • cites Shono et al., 2016 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    PAMPs mature dendritic cells, which then travel to mesenteric lymph nodes and stimulate naive T cells to become CD4+ T cells, including Tregs and Th17 cells.

    “PAMPs act to induce maturation of antigen-presenting cells such as dendritic cells (DCs) as they sample antigen from the lumen”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Lathrop et al., 2011 source

      Not checked in the free run.

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

    Premisecitation

    Humans contain trillions of microbes, comparable in number to human cells, that interact with the host at many sites during development.

    “there are trillions of microbes as numerous as human cells, that interact with the host constantly at numerous sites”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Sender et al., 2016 source

      Not checked in the free run.

    • cites Morgan and Huttenhower, 2012 source

      Not checked in the free run.

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

    Premisecitation

    Dysbiosis is marked by a less diverse and less stable microbiota with possible enrichment of opportunistic pathogenic bacteria.

    “dysbiosis, which is characterized by a less diverse and less stable microbiota, with potential enrichment of opportunistic pathogenic bacteria”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Frosali et al., 2015

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In mice, Lactobacillus rhamnosus GG alone or with Ciprofloxacin before and during transplant reduced GVHD rates and improved overall survival.

    “The administration of the probiotic Lactobacillus rhamnosus GG alone or in combination with Ciprofloxacin before and during transplantation in mice was associated with reduced rates of GVHD and improved overall survival”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Gerbitz et al., 2004 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Treatment-limiting toxicity rates with immune checkpoint blockade are 16% for anti-PD-1, 27% for anti-CTLA-4 and 65% for combination therapy.

    “treatment-limiting toxicity with anti-PD-1 (16%), anti-CTLA-4 (27%), and combination therapies (65%)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Larkin et al., 2015 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Disrupting the gut microbiota with antibiotics may impair anti-tumor immune responses and response to immune checkpoint blockade.

    “This suggests that disrupting the gut microbiota (via antibiotic use) could potentially impair anti-tumor immune responses as well as response to immune checkpoint blockade”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Routy et al., 2018 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Anti-CTLA-4 efficacy is markedly reduced in germ-free mice and in specific-pathogen-free mice given broad-spectrum antibiotics.

    “The efficacy of anti-CTLA-4 therapy was markedly reduced in GF mice and SPF mice with broad-spectrum antibiotics.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Vetizou et al., 2015 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Acute GVHD onset is associated with loss of microbial diversity, reduction of Faecalibacterium, Ruminococcus, Lactobacillus and Blautia, and enrichment of Enterococcus and Clostridiales.

    “The onset of acute-GVHD is associated with significant shifts in the composition of the microbiota with a loss of overall diversity and reduction of health-promoting obligate anaerobes such as Faecalibacterium, Ruminococcus, Lactobacillus, and Blautia, and an enrichment of Enterococcus and Clostridiales”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Jenq et al., 2012 source

      Not checked in the free run.

    • cites Biagi et al., 2015 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    These effects were mediated by increased CD8+ T cell densities and reduced FoxP3+CD4+ Tregs in the tumor microenvironment.

    “These effects were mediated by increased densities of CD8+ T-cells and reduced FoxP3+CD4+ Tregs in the tumor microenvironment”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Matson et al., 2018 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Initial evidence on gut microbiota and immunotherapy came from mouse models, and many findings were later validated in patient cohorts receiving immune checkpoint blockade.

    “Important initial insights came from murine models (Sivan et al., 2015, Vetizou et al., 2015), and many of these findings have now been validated in several patient cohorts treated with immunotherapy, specifically immune checkpoint blockade.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Sivan et al., 2015 source

      Not checked in the free run.

    • cites Vetizou et al., 2015 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A. muciniphila administration increased intra-tumoral immune infiltrates through CCR9+CXCR3+CD4+ T cell recruitment and increased the ratio of CD4+ T cells to CD4+FoxP3+ Tregs during PD1 blockade.

    “administration of A. muciniphilia in these mice was associated with increased intra-tumoral immune infiltrates mediated by the recruitment of CCR9+CXCR3+CD4+ T cells into the tumor bed and increased ratio of CD4+ T-cells to CD4+FoxP3+ T-cells (Tregs) in response to PD1 blockade”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Routy et al., 2018 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Immune responses to cyclophosphamide depend on MyD88 and TLR signaling, suggesting a role for commensal microorganisms.

    “Immune responses to cyclophosphamide have also been shown to be dependent on MyD88 and TLR signaling - suggesting that commensal microorganisms may play a role.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Viaud et al., 2013 source

      Not checked in the free run.

    • cites Iida et al., 2013 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Germ-free mice receiving FMT from responders had delayed tumor outgrowth and enhanced response to immune checkpoint blockade.

    “mice receiving FMT from R had significantly delayed tumor outgrowth and enhanced response to treatment with immune checkpoint blockade”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Gopalakrishnan et al., 2018 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In metastatic melanoma, non-responders to anti-PD-1 had lower gut bacterial diversity and higher abundance of Bacteroidales.

    “NR had significantly lower diversity of gut bacteria and higher abundance of Bacteroidales”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Gopalakrishnan et al., 2018 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Transfer of responder stool to germ-free mice recapitulated the phenotype, with slower tumor growth and improved anti-PD-L1 efficacy compared with non-responder stool.

    “mice that received responder-stool growing tumors at slower rate and having markedly improved efficacy to anti-PD- L1 immunotherapy when compared to mice that received non-responder stool”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Matson et al., 2018 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The effects of cyclophosphamide and other chemotherapy regimens are abrogated in germ-free or antibiotic-treated mice and are differentially affected by particular bacterial species.

    “the effects of cyclophosphamide and other chemotherapy regimens were abrogated in GF or antibiotic- treated mice and were differentially impacted by the presence of particular bacterial species”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Viaud et al., 2013 source

      Not checked in the free run.

    • cites Iida et al., 2013 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In metastatic melanoma, responders to anti-PD-1 had higher gut bacterial diversity and higher relative abundance of Clostridiales, Ruminococcaceae and Faecalibacterium.

    “patients who responded to anti-PD-1 therapy had a significantly higher diversity of bacteria in their gut microbiota as well as a higher relative abundance of Clostridiales, Ruminococcaceae, and Faecalibacterium”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Gopalakrishnan et al., 2018 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The available data strongly indicate that the gut microbiota can modulate anti-tumor immune responses and responses to immune checkpoint blockade.

    “these data provide strong evidence that the gut microbiota can modulate anti-tumor immune responses and responses to immune checkpoint blockade.”
    Quote in the paperSubstantial claim

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

    Interpretationreasoning

    Because these bacteria are relevant to cancer therapy, diet might be a strategy to improve outcomes by modulating the microbiome.

    “Given the importance of these bacteria in implications for cancer therapy, it’s possible that diet could serve as a possible strategy to improve outcomes through modulation of the microbiome.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Dietary intake can shape the composition of the microbiome, and substantial changes in diet can rapidly and significantly alter the gut microbiota.

    “dietary intake can also promote differential composition of the microbiome, with evidence that profound and intensive changes in dietary regimens can significantly alter the gut microbiota in a relatively short amount of time (David et al., 2014).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites David et al., 2014 source

      Not checked in the free run.

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

    Interpretationnone given

    Dietary and lifestyle factors may explain some of the variation in bacterial taxa seen across the studies.

    “dietary and lifestyle factors may also account for some of the differences in bacterial taxa observed across the studies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    FMT has been used in other patient populations and has shown significant success in curing C. difficile infection that is resistant to conventional therapies.

    “FMT has already been employed in other patient populations, showing significant success in curing C. difficile infection resistant to conventional therapies (Borody et al., 2004).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Borody et al., 2004 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Dietary fiber strongly affects gut microbiome composition; reducing fiber intake in healthy people lowers the abundance of immune-promoting F. prausnitzii and the short-chain fatty acid butyrate in stool.

    “Dietary fiber is one component that has been shown to have a profound influence on the composition of the gut microbiome, with a decrease in the abundance of immune-promoting F. prausnitzii (Benus et al., 2010) and the SCFA butyrate in stool samples after reducing dietary fiber in healthy human subjects.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Benus et al., 2010 source

      Not checked in the free run.

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

    Interpretationreasoning

    Geographical influences may also contribute to differences in the observed bacterial taxa, as the studies were conducted in centers around the world.

    “Geographical influences also may exist, as these studies were performed in centers at different locations around the world.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Existing literature has characterized how specific bacterial groups and their metabolites respond to various nutrients and immune parameters, offering initial evidence that dietary modulation might enrich the gut microbiome and immune health.

    “The current body of literature in this area has mapped the responsiveness of specific 15 bacterial groups and their downstream metabolites to a variety of nutrients and immune parameters and provides preliminary insight into how dietary modulation could be used as a strategy to enrich the gut microbiome and immune health (Ma et al., 2018, Shortt et al., 2018)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Ma et al., 2018

      Not checked in the free run.

    • cites Shortt et al., 2018 source

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Premisecitation

    At lower taxonomic levels, the general patterns do not hold: some Firmicutes taxa such as Roseburia and Streptococcus are associated with lack of response, and some Bacteroidetes taxa such as Alistipes, Porphyromonas pasteri and Colinsella aerofaciens are associated with response.

    “at lower levels of taxonomy within these phyla these generalizations do not apply, as some taxa within Firmicutes have been associated with a lack of response (Roseburia, Streptococcus)”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Frankel et al., 2017 source

      Not checked in the free run.

    • cites Matson et al., 2018 source

      Not checked in the free run.

    • cites Routy et al., 2018 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Certain Bacteroidetes taxa have been linked to response to cancer immunotherapy, including Akkermansia muciniphila, Bifidobacterium longum, Bifidobacterium adolescentis, and Colinsela aerofaciens, while others such as Actinomyces viscosus and Gardnerella vaginalis have been linked to non-response.

    “Bacteroidetes have also been associated with response (such as Akkermansia muciniphila, Bifidobacterium longum and Bifidobacterium adolescentis, and Colinsela aerofaciens) and non-response (such as Actinomyces viscosus, Garnderella vaginalis) (Frankel et al., 2017, Gopalakrishnan et al., 2018, Matson et al., 2018, Routy et al., 2018).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Frankel et al., 2017 source

      Not checked in the free run.

    • cites Gopalakrishnan et al., 2018 source

      Not checked in the free run.

    • cites Matson et al., 2018 source

      Not checked in the free run.

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

    Premisecitation

    A primary role of the gut microbiota is to assist in digesting food and extracting nutrients that the host cannot metabolize without microbial help.

    “A major function of the gut microbiota is to aid in host food digestion, harvesting key nutrients that the host is incapable of metabolizing without the help of microbes (Backhed et al., 2005).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Backhed et al., 2005 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Bacteroidales taxa are associated with lack of response to immune checkpoint blockade, while higher abundance of these taxa is generally associated with lower toxicity.

    “bacterial taxa within the Bacteroidales order of the Bacteroidetes phylum have been associated with a lack of response to immune checkpoint blockade (Bacteroidales), while a higher abundance of these taxa within the gut are also generally associated with a lower incidence of toxicity”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Chaput et al., 2017 source

      Not checked in the free run.

    • cites Dubin et al., 2016 source

      Not checked in the free run.

    • cites Gopalakrishnan et al., 2018 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Patients with colitis had increased ICOS on effector CD4+ T cells and low levels of Tregs and systemic inflammatory proteins IL-6, IL-8 and sCD25 at baseline, which may relate to microbiome composition.

    “patients with colitis had increased expression of ICOS on the surface of effector CD4+ T-cells and low levels of Tregs and systemic inflammatory proteins such as IL-6, IL-8 and sCD25 in the blood at baseline, which may be related to the compositional differences in the microbiome”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Chaput et al., 2017 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Several probiotic trials in cancer patients have been initiated, with most focusing on safety and biomarker endpoints and only a minority using cancer-related outcomes such as disease-free survival as a primary endpoint.

    “Several trials using probiotics in cancer patients have been initiated with some completed, and most studies have focused on safety and biomarker-related endpoints, with a minority including cancer- related outcomes (such as disease-free survival) as a primary endpoint (NCT02079662).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites NCT02079662

      Not checked in the free run.

41 of 41

  • The paper relies on this without support.

    Effective conventional chemotherapy requires intact immune responses.

    “effective treatment with conventional chemotherapy is also dependent on intact immune responses”

  • The paper relies on this without support.

    GVHD susceptibility varies with the conditioning regimen, HLA mismatch and donor cell activation status.

    “GVHD susceptibility varies with the type and extent of conditioning regimen, the degree of human leukocyte antigen (HLA) mismatch, and the activation status of donor cells.”

  • The paper relies on this without support.

    A significant fraction of patients receiving immune checkpoint inhibitors do not have objective or durable responses.

    “a significant proportion of patients do not experience objective responses, and when responses do occur, may not be durable”

  • The paper relies on this without support.

    Allogeneic stem cell transplant is one of the earliest effective forms of cancer immunotherapy.

    “Though stem cell transplant may be considered one of the earliest effective forms of cancer immunotherapy”

  • The paper relies on this without support.

    Dietary interventions for modulating the gut microbiota tend to have modest effects, and patient compliance is difficult to enforce and monitor.

    “While dietary interventions may seem relatively simple to design and implement, the effects on the microbiota can be modest, and patient compliance is difficult to enforce and monitor.”
5 of 5

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?

  • Beneficial gut microbes improve the antitumor effects of certain therapies such as ICIs by modulating the immune response.

    “For example, beneficial gut microbes have been shown to improve the antitumor effects of certain therapies such as ICIs by modulating the immune response.333–335”

    From Drug repurposing for cancer therapy (2024) · cites this paper as [333]

  • Microbiome-immune interactions are implicated in a variety of non-communicable gastrointestinal diseases including IBD and celiac disease, as well as extra-intestinal disorders ranging from rheumatic arthritis, metabolic syndrome, neurodegenerative disorder to malignancy.

    “In addition to regulation of infection and commensal spread, microbiome-immune interactions are implicated in a variety of ‘non-communicable’ gastrointestinal diseases including inflammatory bowel disease (IBD)8 and celiac diseases,9 as well as extra-intestinal disorders ranging from rheumatic arthritis,10 metabolic syndrome,11 neurodegenerative disorder12 to malignancy.13”

    From Interaction between microbiota and immunity in health and disease (2020) · cites this paper as [13]

  • Anti-cancer treatment might shape the patient's microbiome and host-specific microbiome can deeply affect patient's response to therapy.

    “Moreover, the very same anti-cancer treatment might shape the patient’s microbiome and, at the same time, host’s specific microbiome can deeply affect patient’s response to therapy [19].”

    From Gut Microbiota and Cancer: From Pathogenesis to Therapy (2019) · cites this paper as [19]

  • The patient's microbiome composition affects the efficacy of both chemotherapy and immunotherapy.

    “These two effects combined together may explain the strong involvement of the patient’s microbiome composition in affecting the efficacy of both chemotherapy and immunotherapy [19].”

    From Gut Microbiota and Cancer: From Pathogenesis to Therapy (2019) · cites this paper as [19]

  • The role of the gut microbiota in shaping the complete immune system has become indisputable.

    “Overall, the role of the gut microbiota in shaping the complete immune system has become indisputable [10].”

    From Probiotics Regulate Gut Microbiota: An Effective Method to Improve Immunity (2021) · cites this paper as [10]

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.

  • A mouse study is described as evidence from patients

    Minor

    The cited 1974 study is titled as an experiment in allogeneic mouse radiation chimeras, but the discussion describes it as an early study of patients treated before HSCT.

1 of 1

Cites

Flagged first, then by citations

1 of the 73 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Related

Authors
Gopalakrishnan, V., Helmink, B. A., Spencer, C. N., Reuben, A., & Wargo, J. A.
Affiliations
The University of Texas MD Anderson Cancer Center (US)
Corresponding author
Wargo, Jennifer A.
ORCID
Venue
Cancer Cell
Publisher
Elsevier BV
Published
2018-04
Volume
33
Issue
4
Pages
570-580
ISSN
1535-6108 (ISSN-L)
DOI
10.1016/j.ccell.2018.03.015
PMC
PMC6529202
OpenAlex
W2797443945
Semantic Scholar
ef32f345e706cb0acf41fe704865c7dd29e8bef1
Cited by
1,392
References
73
Citations by year
2026: 128 · 2025: 171 · 2024: 172 · 2023: 206 · 2022: 219 · 2021: 217 · 2020: 162 · 2019: 89 · 2018: 26
FWCI
12.06
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancer Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • University of Texas MD Anderson Cancer Center
  • Stand Up To Cancer (SU2C-AACR-IRG-19-17)
  • Melanoma Research Alliance (4022024)
  • U.S. Department of Defense (W81XWH-16-1-0121)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
Keywords
gut microbiota, cancer, immunity, cancer immunotherapy, microbiota modulation, precision medicine
MeSH terms
Gastrointestinal Microbiome, Bacteria, Clinical Trials as Topic, Humans, Immunotherapy, Neoplasms, Monitoring, Immunologic, Probiotics, Precision Medicine

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-07.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-07.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review