The DOI matches its Crossref record; 72 of the 73 references it cites were found in a registry or an index; none of the 128 sources its claims cite is checked for support yet.
The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy
Open accessAbstract
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.
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89 Not checked yet · 12 Own interpretation · 1 No basis given
In the paper
“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”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The microbiome and immunity
What the sources say
- Not checked yetcites Stary et al., 2015 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“health-promoting bacteria such as Faecalibacterium and Ruminococcus were reduced”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and stem cell transplantation
What the sources say
- Not checked yetcites Biagi et al., 2015 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“there is compelling evidence that the microbiota helps to shape the immune system as a whole”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The microbiome and immunity
What the sources say
- Not checked yetcites Honda and Littman, 2016
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“There is mounting evidence supporting the role of the microbiome in response to cancer therapy”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > Introduction
What the sources say
boostedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“several recent studies demonstrating the influence of the gut microbiome specifically on the response to immune checkpoint blockade across cancer types”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > Introduction
What the sources say
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“there is now mounting data from human cohorts suggesting that the gut microbiota is a dominant force in mediating both response and toxicity to these therapeutic strategies”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“low levels of 3-indoxyl sulphate in the urine, a by-product of L-tryptophan metabolism by commensal microbiota and a marker for bacterial dysbiosis, was found to be associated with worse overall survival following allo- HSCT”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and stem cell transplantation
What the sources say
- Not checked yetcites Weber et al., 2015 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“some bacterial species have been shown to drive Treg development via alternative pathways dependent on polysaccharide A and TLR signaling to dendritic cells”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The microbiome and immunity
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“markers of response to cancer therapy have continued to evolve and now include factors well beyond established tumor-centric markers”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > Cancer immunosurveillance and response to cancer therapy
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Th17 cells that emigrate can have significant plasticity in function, changing their cytokine output based on the existing local inflammatory or non-inflammatory state”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The microbiome and immunity
What the sources say
- Not checked yetcites Hirota et al., 2011 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 37
- Probably not a substantial claim. 6
- The quote only partly states this claim. 1
In the paper
“cytokine secretion from Th17 cells stimulates IECs to form tight junctions and to secrete anti-microbial proteins”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The microbiome and immunity
What the sources say
- Not checked yetcites Weaver et al., 2013 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“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”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and stem cell transplantation
What the sources say
- Not checked yetcites Taur et al., 2014 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“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”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The microbiome and immunity
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“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”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The microbiome and immunity
What the sources say
- Not checked yetcites Levy et al., 2017 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Th17 cells are markedly depleted in GF animals and can be induced by specific bacterial subsets such as segmented filamentous bacteria (SFB)”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The microbiome and immunity
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“SCFAs here function in a manner dependent on their ability to inhibit histone deacetylase activity suggesting epigenetic regulation”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The microbiome and immunity
What the sources say
- Not checked yetcites Rooks and Garrett, 2016
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“IgA acts primarily by blocking bacterial adherence to epithelial cells; agglutination, entrapment and clearance; and also has direct effects on bacterial virulence”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The microbiome and immunity
What the sources say
- Not checked yetcites Mantis et al., 2011 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“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”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The microbiome and immunity
What the sources say
- Not checked yetcites Abt et al., 2012 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and stem cell transplantation
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and stem cell transplantation
What the sources say
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“PAMPs act to induce maturation of antigen-presenting cells such as dendritic cells (DCs) as they sample antigen from the lumen”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The microbiome and immunity
What the sources say
- Not checked yetcites Lathrop et al., 2011 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“there are trillions of microbes as numerous as human cells, that interact with the host constantly at numerous sites”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The microbiome and immunity
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“dysbiosis, which is characterized by a less diverse and less stable microbiota, with potential enrichment of opportunistic pathogenic bacteria”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The microbiome and immunity
What the sources say
- Not checked yetcites Frosali et al., 2015
hedged- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“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”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and stem cell transplantation
What the sources say
- Not checked yetcites Gerbitz et al., 2004 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“treatment-limiting toxicity with anti-PD-1 (16%), anti-CTLA-4 (27%), and combination therapies (65%)”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and immunotherapy
What the sources say
- Not checked yetcites Larkin et al., 2015 source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“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”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and immunotherapy
What the sources say
- Not checked yetcites Routy et al., 2018 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“The efficacy of anti-CTLA-4 therapy was markedly reduced in GF mice and SPF mice with broad-spectrum antibiotics.”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and immunotherapy
What the sources say
- Not checked yetcites Vetizou et al., 2015 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and stem cell transplantation
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“These effects were mediated by increased densities of CD8+ T-cells and reduced FoxP3+CD4+ Tregs in the tumor microenvironment”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and immunotherapy
What the sources say
- Not checked yetcites Matson et al., 2018 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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.”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and immunotherapy
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“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”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and immunotherapy
What the sources say
- Not checked yetcites Routy et al., 2018 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Immune responses to cyclophosphamide have also been shown to be dependent on MyD88 and TLR signaling - suggesting that commensal microorganisms may play a role.”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and immunotherapy
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“mice receiving FMT from R had significantly delayed tumor outgrowth and enhanced response to treatment with immune checkpoint blockade”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and immunotherapy
What the sources say
- Not checked yetcites Gopalakrishnan et al., 2018 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“NR had significantly lower diversity of gut bacteria and higher abundance of Bacteroidales”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and immunotherapy
What the sources say
- Not checked yetcites Gopalakrishnan et al., 2018 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“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”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and immunotherapy
What the sources say
- Not checked yetcites Matson et al., 2018 source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and immunotherapy
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and immunotherapy
What the sources say
- Not checked yetcites Gopalakrishnan et al., 2018 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“these data provide strong evidence that the gut microbiota can modulate anti-tumor immune responses and responses to immune checkpoint blockade.”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and immunotherapy
boostedconditional- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > Manipulating the gut microbiota to improve responses to therapy > Diet
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“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).”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > Manipulating the gut microbiota to improve responses to therapy > Diet
What the sources say
- Not checked yetcites David et al., 2014 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“dietary and lifestyle factors may also account for some of the differences in bacterial taxa observed across the studies.”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and immunotherapy
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“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).”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > Manipulating the gut microbiota to improve responses to therapy > Fecal Microbiota Transplant (FMT)
What the sources say
- Not checked yetcites Borody et al., 2004 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“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.”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > Manipulating the gut microbiota to improve responses to therapy > Diet
What the sources say
- Not checked yetcites Benus et al., 2010 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Geographical influences also may exist, as these studies were performed in centers at different locations around the world.”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and immunotherapy
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“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)”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > Manipulating the gut microbiota to improve responses to therapy > Diet
What the sources say
- Not checked yetcites Ma et al., 2018
- Not checked yetcites Shortt et al., 2018 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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)”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and immunotherapy
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one. The quote only partly states this claim.
None of the sources cited for this claim have been checked yet.
In the paper
“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).”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and immunotherapy
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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).”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > Manipulating the gut microbiota to improve responses to therapy > Diet
What the sources say
- Not checked yetcites Backhed et al., 2005 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“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”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and immunotherapy
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and immunotherapy
What the sources say
- Not checked yetcites Chaput et al., 2017 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“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).”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > Manipulating the gut microbiota to improve responses to therapy > Administration of bacterial consortia or “designer probiotics”
What the sources say
- Not checked yetcites NCT02079662
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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.”
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?
The cited source says what the claim attributes to it.
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“Gut barrier dysfunction is also strongly correlated with other autoimmune, inflammatory, and metabolic diseases such as diabetes, obesity, atherosclerosis, heart failure, hypertension, and food allergies, as well as with cancer.10,11”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (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.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > The gut microbiota in response and toxicity to immunotherapy > The gut microbiota and stem cell transplantation
“early studies demonstrating reduced rates of GVHD in patients treated with broad-spectrum antibiotics prior to HSCT (van Bekkum et al., 1974)”
§ The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy > References
“64. VAN BEKKUM DW, ROODENBURG J, HEIDT PJ & VAN DER WAAIJ D 1974 Mitigation of secondary disease of allogeneic mouse radiation chimeras by modification of the intestinal microflora.”
Citations
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BackgroundElements of cancer immunity and the cancer–immune set point
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BackgroundHost-Bacterial Mutualism in the Human Intestine
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MethodGut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients
Gopalakrishnan, V., Spencer, C. N., Nezi, L., Reuben, A., Andrews, M. C., Karpinets, T. V., Prieto, P. A., Vicente, D., Hoffman, K., Wei, S. C., et al. (2018) · Science · doi:10.1126/science.aan4236 · Cited by 4,812
Self-citationInduction of Intestinal Th17 Cells by Segmented Filamentous Bacteria
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BackgroundGenetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma
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Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy
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Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota
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“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 patient cohorts treated with immunotherapy, specifically immune checkpoint blockade.”
BackgroundResultInfluentialGut microbiota, metabolites and host immunity
Rooks, M. G., & Garrett, W. S. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.42 · Cited by 3,409 · cited 1×
“…and mucosal T cells (such as Tregs), as maintenance of these cells at the level of the gut is facilitated by bacterial metabolites such as SCFAs; the fuction of SCFAs is dependent on their ability to inhibit histone deacetylase activity suggesting epigenetic regulation (Rooks and Garrett, 2016).”
BackgroundThe commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients
Matson, V., Fessler, J., Bao, R., Chongsuwat, T., Zha, Y., Alegre, M.-L., Luke, J. J., & Gajewski, T. F. (2018) · Science · doi:10.1126/science.aao3290 · Cited by 3,107
Commensal Bacteria Control Cancer Response to Therapy by Modulating the Tumor Microenvironment
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“Indeed, the effects of cyclophosphamide and other chemotherapy regimens were abrogated in GF or antibiotic-treatedmice andwere differentially affected by the presence of particular bacterial species (Viaud et al., 2013; Iida et al., 2013).”
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“Furthermore, oral feeding with Bacteroides fragilis in combination with either Bacteroides thetaiotaomicron or Burkholderia cepacia augmented the action of anti-CTLA-4 therapy by eliciting a Th1 response in the lymph nodes and facilitating the maturation of intra-tumoral DCs.”
BackgroundInfluentialThe Intestinal Microbiota Modulates the Anticancer Immune Effects of Cyclophosphamide
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The microbiota in adaptive immune homeostasis and disease
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“Overall, there is compelling evidence that the microbiota help to shape the immune system as a whole (Honda and Littman, 2016).”
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Dysbiosis and the immune system
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BackgroundFate mapping of IL-17-producing T cells in inflammatory responses
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Peripheral education of the immune system by colonic commensal microbiota
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“Analyses of longitudinal fecal samples demonstrated a disruption of the existing state of equilibrium of the gut microbiota postHSCT, with a loss of bacterial diversity and stability, and dominance of Enterococcus, Streptococcus, and various Proteobacteria (Holler et al., 2014; Taur et al., 2012).”
BackgroundCommensal bacteria calibrate the activation threshold of innate antiviral immunity
Abt, M. C., Osborne, L. C., Monticelli, L. A., Doering, T. A., Alenghat, T., Sonnenberg, G. F., Paley, M. A., Antenus, M., Williams, K. L., Erikson, J., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.04.011 · Cited by 993 · cited 2×
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BackgroundDubin, K., Callahan, M. K., Ren, B., Khanin, R., Viale, A., Ling, L., No, D., Gobourne, A., Littmann, E., Huttenhower, C., et al. (2016) · Nature Communications · doi:10.1038/ncomms10391 · Cited by 987 · cited 6×
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BackgroundMethodInfluentialSystemic Immunity Is Required for Effective Cancer Immunotherapy
Spitzer, M. H., Carmi, Y., Reticker-Flynn, N. E., Kwek, S. S., Madhireddy, D., Martins, M. M., Gherardini, P. F., Prestwood, T. R., Chabon, J., Bendall, S. C., et al. (2017) · Cell · doi:10.1016/j.cell.2016.12.022 · Cited by 963 · cited 1×
“Recent evidence substantiates the need for preserved overall systemic immunity in mediating responses to immunotherapy specifically (Chen and Mellman, 2013, 2017; Spitzer et al., 2017).”
BackgroundTaur, Y., Jenq, R. R., Perales, M.-A., Littmann, E. R., Morjaria, S., Ling, L., No, D., Gobourne, A., Viale, A., Dahi, P. B., et al. (2014) · Blood · doi:10.1182/blood-2014-02-554725 · Cited by 885 · cited 1×
“…in long-term survival, with patients having a lower diversity of microbiota in their gut at the time of HSCT having shortened overall survival and higher mortality rates (specifically transplantrelated mortality), compared with those with a high diversity of gut microbiota (Taur et al., 2014).”
BackgroundCombined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma
Valsecchi, M. E. (2015) · New England Journal of Medicine · doi:10.1056/nejmc1509660 · Cited by 874 · cited 1×
“(Larkin et al., 2015).”
Ramirez-Farias, C., Slezak, K., Fuller, Z., Duncan, A., Holtrop, G., & Louis, P. (2008) · British Journal of Nutrition · doi:10.1017/s0007114508019880 · Cited by 822
Intestinal Blautia Is Associated with Reduced Death from Graft-versus-Host Disease
Jenq, R. R., Taur, Y., Devlin, S. M., Ponce, D. M., Goldberg, J. D., Ahr, K. F., Littmann, E. R., Ling, L., Gobourne, A. C., Miller, L. C., et al. (2015) · Biology of Blood and Marrow Transplantation · doi:10.1016/j.bbmt.2015.04.016 · Cited by 748 · cited 4×
“A high abundance of the genus Blautia of the Clostridia class was found to be associated with reduced GVHD lethality in two independent cohorts of patients undergoing treatment with allo-HSCT (Jenq et al., 2015).”
BackgroundInfluentialBlank, C. U., Haanen, J. B., Ribas, A., & Schumacher, T. N. (2016) · Science · doi:10.1126/science.aaf2834 · Cited by 748 · cited 3×
“…including ‘‘foreignness’’ (includingmutational load) (Snyder et al., 2014), aspects of tumor metabolism (such as glucose metabolism), and factors affecting tumor sensitivity to immune effectors (including human leukocyte antigen [HLA] and interferon gamma gene expression) (Blank et al., 2016).”
BackgroundOuter Membrane Vesicles of a Human Commensal Mediate Immune Regulation and Disease Protection
Shen, Y., Torchia, M. L. G., Lawson, G. W., Karp, C. L., Ashwell, J. D., & Mazmanian, S. K. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.08.004 · Cited by 714 · cited 1×
“In addition, some bacterial species have been shown to drive Treg development via alternative pathways dependent on polysaccharide A and TLR signaling to DCs (Round and Mazmanian, 2010; Shen et al., 2012).”
BackgroundFrankel, A. E., Coughlin, L. A., Kim, J., Froehlich, T. W., Xie, Y., Frenkel, E. P., & Koh, A. Y. (2017) · Neoplasia · doi:10.1016/j.neo.2017.08.004 · Cited by 709 · cited 11×
“However, at lower levels of taxonomy, these generalizations do not apply, as some taxa within Firmicutes have been associated with a lack of response (Roseburia, Streptococcus) (Frankel et al., 2017; Matson et al., 2018) and some taxa within Bacteroidetes have been associated with response (Alistipes, Porphyromonas pa…”
BackgroundMethodResultInfluentialNew concepts in the generation and functions of IgA
Pabst, O. (2012) · Nature reviews. Immunology · doi:10.1038/nri3322 · Cited by 656 · cited 1×
“Metabolites produced by bacteria may also affect local immunity via production of short-chain fatty acids (SCFAs), which, among a number of key activities, have been shown to augment immunity via IgA production by plasma cells (Pabst, 2012).”
BackgroundRegulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation
Jenq, R. R., Ubeda, C., Taur, Y., Menezes, C. C., Khanin, R., Dudakov, J. A., Liu, C., West, M. L., Singer, N. V., Equinda, M. J., et al. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20112408 · Cited by 626
Shono, Y., Docampo, M. D., Peled, J. U., Perobelli, S. M., Velardi, E., Tsai, J. J., Slingerland, A. E., Smith, O. M., Young, L. F., Gupta, J., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf2311 · Cited by 592 · cited 15×
“In addition to the relationship to response and survival, the influence of the gut microbiota has also been studied in the context of toxicity to HSCT therapies—particularly with regard to graft-versus-host disease (GVHD).”
BackgroundResultInfluentialPaulos, C. M., Wrzesinski, C., Kaiser, Hinrichs, C. S., Chieppa, M., Cassard, L., Palmer, D. C., Boni, A., Muranski, P., Yu, Z., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32205 · Cited by 586 · cited 1×
“They surmised that the translocation of gut bacteria helped to prime an immune response via TLR4 signaling (Paulos et al., 2007).”
BackgroundNormalization of host intestinal mucus layers requires long-term microbial colonization
Johansson, M. E. V., Jakobsson, H. E., Holmén-Larsson, J., Schütte, A., Ermund, A., Rodríguez-Piñeiro, A. M., Arike, L., Wising, C., Svensson, F., Bäckhed, F., et al. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.10.007 · Cited by 549
Holler, E., Butzhammer, P., Schmid, K., Hundsrucker, C., Koestler, J., Peter, K., Zhu, W., Sporrer, D., Hehlgans, T., Kreutz, M., et al. (2014) · Biology of Blood and Marrow Transplantation · doi:10.1016/j.bbmt.2014.01.030 · Cited by 544 · cited 1×
“Analyses of longitudinal fecal samples demonstrated a disruption of the existing state of equilibrium of the gut microbiota postHSCT, with a loss of bacterial diversity and stability, and dominance of Enterococcus, Streptococcus, and various Proteobacteria (Holler et al., 2014; Taur et al., 2012).”
BackgroundOh, J. Z., Ravindran, R., Chassaing, B., Carvalho, F. A., Maddur, M. S., Bower, M., Hakimpour, P., Gill, K. P., Nakaya, H. I., Yarovinsky, F., et al. (2014) · Immunity · doi:10.1016/j.immuni.2014.08.009 · Cited by 541 · cited 2×
“Specific components of the microbiota can prime the immune 572 Cancer Cell 33, April 9, 2018 systemby activating TLR signaling pathways serving as a natural vaccine adjuvant (Oh et al., 2014).”
BackgroundWeber, J. S., Kudchadkar, R. R., Yu, B., Gallenstein, D., Horak, C. E., Inzunza, H. D., Zhao, X., Martinez, A. J., Wang, W., Gibney, G., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2013.51.4802 · Cited by 535 · cited 2×
“due to mucosal immune dysregulation (Berman et al., 2010; Weber et al., 2013).”
BackgroundChapter 12: Human Microbiome Analysis
Morgan, X. C., & Huttenhower, C. (2012) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002808 · Cited by 496 · cited 1×
“Therefore, it is not surprising that they play such a large role in numerous host functions including immunity (Sender et al., 2016; Morgan and Huttenhower, 2012).”
BackgroundThe Th17 pathway and inflammatory diseases of the intestines, lungs, and skin
Weaver, C. T., Elson, C. O., Fouser, L. A., & Kolls, J. K. (2013) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130318 · Cited by 462 · cited 1×
“Th17 cells also function in mucosal immunity as cytokine secretion from Th17 cells stimulates IECs to form tight junctions and to secrete anti-microbial proteins (Weaver et al., 2013).”
BackgroundStool microbiota and vaccine responses of infants
Huda, M. N., Lewis, Z., Kalanetra, K. M., Rashid, M., Ahmad, S. M., Raqib, R., Qadri, F., Underwood, M. A., Mills, D. A., & Stephensen, C. B. (2014) · PEDIATRICS · doi:10.1542/peds.2013-3937 · Cited by 392 · cited 1×
“A highly diverse microbiota has been associated with improved adaptive immune responses to a variety of vaccines in infants (Huda et al., 2014).”
BackgroundA mucosal vaccine against Chlamydia trachomatis generates two waves of protective memory T cells
Stary, G., Olive, A., Radovic-Moreno, A. F., Gondek, D., Alvarez, D., Basto, P. A., Perro, M., Vrbanac, V. D., Tager, A. M., Shi, J., et al. (2015) · Science · doi:10.1126/science.aaa8205 · Cited by 379 · cited 1×
“…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 against the same organism or against other antigens by crossreaction to similar epitopes (Stary et al., 2015).”
BackgroundFaith, J. J., Ahern, P. P., Ridaura, V. K., Cheng, J., & Gordon, J. I. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3008051 · Cited by 373 · cited 1×
“This may be related to the known influence of these bacteria in Treg differentiation (Round and Mazmanian, 2010; Faith et al., 2014).”
BackgroundHibberd, A. A., Lyra, A., Ouwehand, A. C., Rolny, P., Lindegren, H., Cedgård, L., & Wettergren, Y. (2017) · BMJ Open Gastroenterology · doi:10.1136/bmjgast-2017-000145 · Cited by 373 · cited 2×
“This includes a trial where patients with CRC were treated with probiotics containing strains of Lactobacillus acidophilus and Bifidobacterium lactis, and were shown to have an increased abundance of butyrate-producing bacteria (particularly Faecalibacterium and other Clostridiales) within the tumor, and its associate…”
BackgroundBekkum, D. W. V., Roodenburg, J., Heidt, P. J., & Waaij, D. V. D. (1974) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/52.2.401 · Cited by 330 · cited 10×
“In addition to the relationship to response and survival, the influence of the gut microbiota has also been studied in the context of toxicity to HSCT therapies—particularly with regard to graft-versus-host disease (GVHD).”
ResultInfluentialAcute graft versus host disease
Jacobsohn, D. A., & Vogelsang, G. B. (2007) · Orphanet Journal of Rare Diseases · doi:10.1186/1750-1172-2-35 · Cited by 325
Intestinal Microbiota and Relapse After Hematopoietic-Cell Transplantation
Peled, J. U., Devlin, S. M., Staffas, A., Lumish, M., Khanin, R., Littmann, E. R., Ling, L., Kosuri, S., Maloy, M., Slingerland, J. B., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2016.70.3348 · Cited by 325 · cited 3×
“…varied widely across the studies (Chaput et al., 2017; Dubin et al., 2016; Frankel et al., 2017; Gopalakrishnan et al., 2018; Jenq et al., 2015; Matson et al., 2018; Peled et al., 2017; Routy et al., 2018)—suggesting the importance of developing standardized approaches for microbiome analysis.”
BackgroundBacteriotherapy Using Fecal Flora: Toying With Human Motions
Borody, T. J., Warren, E. F., Leis, S. M., Surace, R., Ashman, O., & Siarakas, S. (2004) · Journal of Clinical Gastroenterology · doi:10.1097/01.mcg.0000128988.13808.dc · Cited by 283
Frosali, S., Pagliari, D., Gambassi, G., Landolfi, R., Pandolfi, F., & Cianci, R. (2015) · Journal of Immunology Research · doi:10.1155/2015/489821 · Cited by 281 · cited 1×
“Disruption of the delicate balance of commensal bacteria is seen in the setting of dysbiosis, which is characterized by a less-diverse and less-stable microbiota, with potential enrichment of opportunistic pathogenic bacteria (Frosali et al., 2015).”
BackgroundNutrients Mediate Intestinal Bacteria–Mucosal Immune Crosstalk
Ma, N., Guo, P., Zhang, J., He, T., Kim, S. W., Zhang, G., & Ma, X. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00005 · Cited by 252
Hallmarks of response to immune checkpoint blockade
Cogdill, A. P., Andrews, M. C., & Wargo, J. A. (2017) · British Journal of Cancer · doi:10.1038/bjc.2017.136 · Cited by 251 · cited 1×
“Tremendous efforts have focused on identifying predictors of the response to immune checkpoint blockade as well as strategies to overcome therapeutic resistance (Cogdill et al., 2017; Sharma et al., 2017).”
BackgroundSelf-citationBerman, D., Parker, S. M., Siegel, J., Chasalow, S. D., Weber, J. S., Galbraith, S. M., Targan, S. R., & Wang, H. L. (2010) · PubMed Central · Cited by 226
Cahn, J. (2005) · Blood · doi:10.1182/blood-2004-11-4557 · Cited by 222 · cited 1×
“Severe acute GVHD has a long-term survival probability of less than 5% (Cahn et al., 2005) and chronic GVHD is also associated with significant morbidity andmortality.”
BackgroundSpiljar, M., Merkler, D., & Trajkovski, M. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01353 · Cited by 219 · cited 1×
“(Johansson et al., 2015; Spiljar et al., 2017).”
Heimesaat, M. M., Nogai, A., Bereswill, S., Plickert, R., Fischer, A., Loddenkemper, C., Steinhoff, U., Tchaptchet, S., Thiel, E., Freudenberg, M. A., et al. (2010) · Gut · doi:10.1136/gut.2009.197434 · Cited by 217
Benus, R. F. J., van der Werf, T. S., Welling, G. W., Judd, P. A., Taylor, M. A., Harmsen, H. J. M., & Whelan, K. (2010) · British Journal Of Nutrition · doi:10.1017/s0007114510001030 · Cited by 210 · cited 1×
“…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 a reduction in dietary fiber intake in healthy human subjects.”
BackgroundWeber, D., Oefner, P. J., Hiergeist, A., Koestler, J., Gessner, A., Weber, M., Hahn, J., Wolff, D., Stämmler, F., Spang, R., et al. (2015) · Blood · doi:10.1182/blood-2015-04-638858 · Cited by 195
Shortt, C., Hasselwander, O., Meynier, A., Nauta, A., Fernández, E. N., Putz, P., Rowland, I., Swann, J., Türk, J., Vermeiren, J., et al. (2018) · European Journal of Nutrition · doi:10.1007/s00394-017-1546-4 · Cited by 194
Probiotic effects on experimental graft-versus-host disease: let them eat yogurt
Gerbitz, A., Schultz, M., Wilke, A., Linde, H.-J., Schölmerich, J., Andreesen, R., & Holler, E. (2004) · Blood · doi:10.1182/blood-2003-11-3769 · Cited by 186 · cited 4×
“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 (Gerbitz et al., 2004).”
BackgroundInfluentialGut microbiota trajectory in pediatric patients undergoing hematopoietic SCT
Biagi, E., Zama, D., Nastasi, C., Consolandi, C., Fiori, J., Rampelli, S., Turroni, S., Centanni, M., Severgnini, M., Peano, C., et al. (2015) · Bone Marrow Transplantation · doi:10.1038/bmt.2015.16 · Cited by 158
The breakthrough of the microbiota
Kroemer, G., & Zitvogel, L. (2018) · Nature Reviews Immunology · doi:10.1038/nri.2018.4 · Cited by 147 · cited 1×
“In addition, recent insights importantly highlight the impact of microbiota (particularly the gut microbiota) on responses across several cancer therapies (Kroemer and Zitvogel, 2018).”
BackgroundHuys, G., Botteldoorn, N., Delvigne, F., De Vuyst, L., Heyndrickx, M., Pot, B., Dubois, J., & Daube, G. (2013) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201300065 · Cited by 132 · cited 1×
“Certainly, there is wide variability in probiotic formulations available with regard to their composition, stability, and authenticity (Huys et al., 2013); thus significant caution should be taken in advocating their use to cancer patients until these can be carefully tested.”
BackgroundConsoli, M. L. D., da Silva, R. S., Nicoli, J. R., Bruña‐Romero, O., da Silva, R. G., de Vasconcelos Generoso, S., & Correia, M. I. T. D. (2016) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607115584387 · Cited by 93 · cited 2×
“…immunity in CRC patients, demonstrating altered cytokine profiles within the colonic mucosa at the time of colon resection, with lower IL-1b, IL-10, and IL-23A mRNA levels in the patients treated with probiotics comparedwith controls who received no probiotics (NCT01895530) (Consoli et al., 2016).”
BackgroundRouty, B., Letendre, C., Enot, D., Chénard-Poirier, M., Mehraj, V., Séguin, N. C., Guenda, K., Gagnon, K., Woerther, P.-L., Ghez, D., et al. (2017) · OncoImmunology · doi:10.1080/2162402x.2016.1258506 · Cited by 75 · cited 13×
“In addition to the relationship to response and survival, the influence of the gut microbiota has also been studied in the context of toxicity to HSCT therapies—particularly with regard to graft-versus-host disease (GVHD).”
BackgroundInfluential
Cited by
Sorted by citations
Hallmarks of Cancer: New Dimensions
Hanahan, D. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-1059 · Cited by 9,887
“Beyond the causal links to colon cancer and melanoma, the gut microbiome’s demonstrable ability to elicit the expression of immunomodulatory chemokines and cytokines that enter the systemic circulation is evidently also capable of affecting cancer pathogenesis and response to therapy in other organs of the body (94, 9…”
BackgroundInteraction between microbiota and immunity in health and disease
Zheng, D., Liwinski, T., & Elinav, E. (2020) · Cell Research · doi:10.1038/s41422-020-0332-7 · Cited by 3,947
“microbiome in anticancer immune surveillance and immunotherapy may hold great promise in optimizing treatment responses in cancer patients, and has been reviewed elsewhere in greater detail.(13,196) Aside from the gut microbiome, most recent research begins to explore the role of intra-tumor tissue microbiome in regul…”
BackgroundCancer immunoediting and resistance to T cell-based immunotherapy
O’Donnell, J. S., Teng, M. W. L., & Smyth, M. J. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0142-8 · Cited by 1,826
Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients
Baruch, E. N., Youngster, I., Ben-Betzalel, G., Ortenberg, R., Lahat, A., Katz, L., Adler, K., Dick-Necula, D., Raskin, S., Bloch, N., et al. (2021) · Science · doi:10.1126/science.abb5920 · Cited by 1,757
Self-citationThe microbiome and human cancer
Sepich-Poore, G. D., Zitvogel, L., Straussman, R., Hasty, J., Wargo, J. A., & Knight, R. (2021) · Science · doi:10.1126/science.abc4552 · Cited by 1,332
“Although most proposed cancer-microbe relationships focus on gut microbiota (30, 32, 33), recent studies also contentiously suggest the existence, metabolic activity, and functional importance of intratumoral microbiota using a combination of imaging, sequencing, and cultivation techniques and genetically engineered a…”
BackgroundSelf-citation
Metadata
- 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)
- 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
- bronze
- doi.org
- 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 › Bacterial Cancer Therapy
- 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
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