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Cited by 2,464Gut microbiota and healthCancer Research and TreatmentsCancer Genomics and Diagnostics

The human tumor microbiome is composed of tumor type–specific intracellular bacteria

Open access
Nejman, Deborah, Livyatan, Ilana, Fuks, Garold, Gavert, Nancy, Zwang, Yaara, Geller, Leore T., Rotter-Maskowitz, Aviva, Weiser, Roi +53 more·2020·Science
DOI 10.1126/science.aay9189PMC PMC7757858
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Abstract

Profiling tumor bacteria: Bacteria are well-known residents in human tumors, but whether their presence is advantageous to the tumors or to the bacteria themselves has been unclear. As an initial step toward addressing this question, Nejman et al. produced an exhaustive catalog of the bacteria present in more than 1500 human tumors representing seven different tumor types (see the Perspective by Atreya and Turnbaugh). They found that the bacteria within tumors were localized within both cancer cells and immune cells and that the bacterial composition varied according to tumor type. Certain biologically plausible associations were identified. For example, breast cancer subtypes characterized by increased oxidative stress were enriched in bacteria that produce mycothiol, which can detoxify reactive oxygen species. Science , this issue p. 973 ; see also p. 938

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Crossref · 10.1126/science.aay9189

Cites

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Claims the paper makes

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  • Findingown data

    LPS and bacterial 16S rRNA were localized mainly in cancer cells and immune cells.

    “Pathological examination of tumor cores indicated that LPS and bacterial 16S rRNA were localized mainly in cancer cells and immune cells”
    Quote in the paperSubstantial claim
  • Findingown data

    Bacterial DNA levels in all tumor types were significantly higher than in DNA extraction and paraffin controls.

    “Levels of bacterial DNA in all tumor types were significantly higher than those found in both DNA extraction and paraffin controls (Fig. 1B; P value <10−10 for each tumor type, Wilcoxon rank sum test).”
    Quote in the paperSubstantial claim
  • Findingown data

    CLEM on four human breast tumors positive for LPS and 16S rRNA demonstrated intracellular localization of bacteria in all four tumors.

    “Combined LPS fluorescence staining and transmission electron microscopy (TEM) imaging of the same cells clearly demonstrated the intracellular localization of bacteria in all four tumors”
    Quote in the paperSubstantial claim
  • Findingown data

    The proportion of tumors positive for bacterial DNA varies by cancer type, from 14.3% in melanoma to more than 60% in breast, pancreatic, and bone tumors.

    “We found that different cancer types vary in the proportion of tumors that are positive for bacterial DNA, ranging from only 14.3% in melanoma to >60% in breast, pancreatic, and bone tumors.”
    Quote in the paperSubstantial claim
  • Findingown data

    LTA-positive bacteria were almost exclusively found in macrophages.

    “LTA-positive bacteria were almost exclusively found in macrophages, as detected by hematoxylin and eosin (H&E) staining and verified by immunofluorescence (IF) for CD68”
    Quote in the paperNot a substantial claim
  • May combine two claims. 20
  • Classified as probably not a substantial claim. 22

  • May combine two claims.

    Findingown data

    Bacterial LPS and 16S rRNA were frequently detected in all tumor types and showed similar spatial distribution.

    “Bacterial LPS and 16S rRNA were frequently detected in all tumor types (Fig. 1C) and demonstrated a similar spatial distribution”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In cancer cells, bacterial 16S rRNA was detected mostly in the cytoplasm, while LPS staining was associated with both cytoplasm and nucleus.

    “In cancer cells, bacterial 16S rRNA was detected mostly in the cytoplasm, whereas LPS staining was associated with both the cytoplasm and the nucleus”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    LTA was detected mainly in melanomas and was largely absent in other tumor types.

    “LTA was detected mainly in melanomas and was largely absent in other tumor types.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Fifteen isolated species (40.5%) were detected in the breast tumor cohort but did not pass all filters.

    “Fifteen isolated species (40.5%) were detected in our breast tumor cohort but did not pass all filters.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    An average of 16.4 bacterial species were detected in any single breast tumor sample, whereas the average was fewer than 9 in all other tumor types.

    “An average of 16.4 bacterial species were detected in any single breast tumor sample, whereas the average was <9 in all other tumor types (P value <10−17 for each tumor type, Wilcoxon rank sum test”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Although Proteobacteria and Firmicutes accounted for most detected bacterial sequences in all cancer types, the Proteobacteria to Firmicutes ratio appears to vary between tumor types.

    “Although species belonging to the Proteobacteria and Firmicutes phyla accounted for most of the detected bacterial sequences in all cancer types, the Proteobacteria to Firmicutes (P/F) ratio appears to vary between tumor types”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    More than 1000 colonies were grown per tumor from four of five fresh breast tumors, and 37 colonies from one tumor.

    “>1000 colonies were grown per tumor from four of the tumors, and 37 colonies were grown from one tumor.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Although overall microbial composition of different tumor types was relatively similar to their NAT microbiome, bacteria with different prevalence in tumors and NAT were detected.

    “although the overall microbial composition of the different tumor types was relatively similar to their NAT microbiome (Fig. 4F), we also detected bacteria with a different prevalence in tumors and in their NAT”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Bacterial load and richness were higher in breast tumor samples than in normal breast samples from healthy subjects.

    “We also found that bacterial load and richness were higher in the breast tumor samples than those found in normal breast samples from healthy subjects.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Whole-genome sequencing of 474 representative colonies from all five tumors demonstrated they represented 37 different bacterial species, 11 of which were previously detected as hits in the breast tumor cohort.

    “Whole-genome sequencing of 474 representative colonies from all five tumors demonstrated that they represented 37 different bacterial species, 11 of which (29.7%) are bacteria that were previously detected as hits in our breast tumor cohort”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Proteobacteria dominated the microbiome of pancreatic cancer, similarly to the normal duodenal microbiome.

    “In contrast, Proteobacteria dominated the microbiome of pancreatic cancer, similarly to the normal duodenal microbiome makeup (16, 17, 48, 49).”
    Quote in the paperSubstantial claim0 of 4 sources checked
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      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Bacteria expressing these functions are found mainly in Proteobacteria, Actinobacteria, and Cyanobacteria phyla, and are depleted from Firmicutes.

    “Bacteria expressing these functions are found mainly in the Proteobacteria, Actinobacteria, and Cyanobacteria phyla, and they are depleted from the Firmicutes phylum”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Predicted MetaCyc pathways from 16S sequences accurately represent the functional capabilities of intratumor bacteria.
    • Rests on an assumption: Patients' smoking status was accurately recorded.

  • May combine two claims.

    Findingown data

    Taxa more abundant in responders included Clostridium, whereas Gardnerella vaginalis was more abundant in nonresponders.

    “Taxa that were more abundant in tumors of responders included Clostridium, whereas Gardnerella vaginalis was more abundant in tumors of nonresponders.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The classification of melanoma patients as responders or nonresponders to immune checkpoint inhibitors is accurate.

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

    Premisecitation

    Intratumor bacteria have been reported in many tumor types.

    “Intratumor bacteria have been reported in many tumor types (2-19)”
    Quote in the paperNot a substantial claim0 of 10 sources checked
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  • May combine two claims.

    Interpretationreasoning

    The rarity of typical bacterial forms and absence of LTA in cancer cells despite many Gram-positive bacteria by sequencing suggests that bacteria in tumor cells may have altered their envelope, perhaps to a cell wall-deficient state akin to L-forms.

    “This observation, combined with the fact that no cell wall polymer LTA was detected in cancer cells—despite the detection of many Gram-positive bacteria in human tumors by 16S rDNA sequencing—suggests that bacteria in tumor cells may have altered their envelope, perhaps leading to a cell wall–deficient state, akin to L-forms (41).”
    Quote in the paperSubstantial claim0 of 1 sources checked
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      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Mechanical tissue shearing in DNA isolation is important to ensure complete recovery of DNA from Gram-positive bacteria.

    “it is also important to use mechanical tissue shearing in the DNA isolation protocol to ensure the complete recovery of DNA from within the cell wall of Gram-positive bacteria—a step not included in most standard DNA isolation protocols (6, 7).”
    Quote in the paperSubstantial claim0 of 2 sources checked
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      Not checked in the free run.

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      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The study included 643 negative controls processed with samples, including 437 DNA extraction controls and 206 PCR no-template controls.

    “we introduced 643 negative controls that were processed with the samples, including 437 DNA extraction controls and 206 polymerase chain reaction (PCR) no-template controls (NTCs).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Processing of bacterial LPS by macrophages is very slow, so LPS can be found months after bacteria were ingested.

    “It has been previously demonstrated that the processing of bacterial LPS by macrophages is very slow; therefore, LPS can be found in these cells months after the bacteria were ingested and processed (38).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [38] Forestier C, Moreno E, Pizarro-Cerda J, Gorvel JP, Lysosomal accumulation and recycling of lipopolysaccharide to the cell surface of murine macrophages, an in vitro and in vivo study. J. Immunol 162, 6784– 6791 (1999). pmid:10352299 10352299 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    The study included 168 paraffin-only samples from margins of paraffin blocks to address pre-laboratory contamination.

    “we also included 168 paraffin-only samples taken from the margins of the paraffin blocks (without tissue) that were used in the study”
    Quote in the paperSubstantial claim

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

    Premisecitation

    The gut microbiome has multiple effects on tumor biology, including transformation, progression, and response to anticancer therapies including immunotherapy.

    “The gut microbiome has been shown to have multiple effects on tumor biology, such as the transformation process, tumor progression, and the response to anticancer therapies including immunotherapy (21-29).”
    Quote in the paperNot a substantial claim0 of 9 sources checked
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      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    IHC-negative and FISH-negative controls were applied to control for nonspecific staining.

    “To control for nonspecific staining, IHC-negative controls (no primary antibody) and FISH-negative controls (nonspecific complement probe) were also applied to the samples”
    Quote in the paperSubstantial claim

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

    Study design and conductreasoning

    The 5R method can be applied to partially degraded DNA from formalin-fixed paraffin-embedded tumors.

    “Moreover, it can be applied to partially degraded DNA originating from formalin-fixed paraffin-embedded tumors.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    A strict set of six filters was applied to control for potential contamination sources.

    “we applied a strict set of six filters to control for potential sources of contamination.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    D-alanine is used by bacteria to generate peptidoglycan but is not used by mammalian cells.

    “Although D-alanine is used by bacteria to generate peptidoglycan, an essential component of the bacterial cell wall, it is not used by mammalian cells (fig. S14) (47).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [47] Siegrist MS, Whiteside S, Jewett JC, Aditham A, Cava F, Bertozzi CR, (D)-Amino acid chemical reporters reveal peptidoglycan dynamics of an intracellular pathogen. ACS Chem. Biol 8, 500– 505 (2013).doi: 10.1021/cb3004995pmid:23240806 23240806 PMC3601600 source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    The 5R 16S rDNA sequencing method amplifies 68% of the bacterial 16S rRNA gene and increases coverage and resolution compared with V4 or V3-V4 amplification.

    “By amplifying 68% of the bacterial 16S rRNA gene using short amplicons, this method increases the coverage and resolution of the detection of bacterial species compared with the widely used V4 or V3-V4 amplification”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Bone collagen is a main source of hydroxyproline, and many bone pathologies, like bone tumors, result in elevated hydroxyproline levels.

    “Bone collagen is a main source of hydroxyproline, and many bone pathologies, like bone tumors, have been shown to result in elevated hydroxyproline levels (53).”
    Quote in the paperSubstantial claim0 of 1 sources checked
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      Not checked in the free run.

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

    Premisecitation

    Cell wall-deficient bacteria are known to be found exclusively inside cells, where their morphology transforms into less-defined structures of variable sizes and shapes.

    “Cell wall–deficient bacteria are known to be found exclusively inside cells, where their morphology transforms into less-defined structures of highly variable sizes and shapes (42, 43).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [42] Errington J, L-form bacteria, cell walls and the origins of life. Open Biol. 3, 120143 (2013).doi: 10.1098/rsob.120143pmid:23303308 23303308 PMC3603455 source

      Not checked in the free run.

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      Not checked in the free run.

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

    Study design and conductnone given

    Thirty-nine samples and 10 controls with fewer than 1000 normalized reads were discarded from further analysis.

    “Thirty-nine samples and 10 controls that had fewer than 1000 normalized reads were discarded from further analysis”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    ER+ breast tumors have increased oxidative stress compared with ER− tumors.

    “Because ER+ breast tumors are known to have increased oxidative stress compared with ER− tumors (57)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [57] Karihtala P, Kauppila S, Soini Y, Arja-Jukkola-Vuorinen, Oxidative stress and counteracting mechanisms in hormone receptor positive, triple-negative and basal-like breast carcinomas. BMC Cancer 11, 262 (2011).doi: 10.1186/1471-2407-11-262 pmid:21693047 21693047 PMC3141776 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted).

    Interpretationreasoning

    Bacteria with the ability to synthesize mycothiol can better survive in the ER+ tumor microenvironment.

    “we hypothesize that bacteria with the ability to synthesize mycothiol can better survive in the ER+ tumor microenvironment.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Predicted MetaCyc pathways from 16S sequences accurately represent the functional capabilities of intratumor bacteria.
    • Rests on an assumption: Breast cancer subtype assignment by ER, PR, and HER2 status is accurate.

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

    Interpretationown data

    A possible source of intratumor bacteria is the adjacent normal tissue (NAT).

    “Intratumor bacteria may also arise from the NAT, which can explain the high similarity we found between the tumor microbiome and its NAT microbiome.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Several steps were taken to limit and manage contamination.

    “We took multiple measures to minimize and control for contamination (supplementary note)”
    Quote in the paperSubstantial claim

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

    Premisecitation

    During tumor growth, leaky and disorganized vessels may let circulating bacteria enter.

    “As tumors develop, their disorganized, leaky vasculature may allow circulating bacteria to enter, and the immunosuppressed environment may provide a refuge for them (61, 62).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [61] Cummins J, Tangney M, Bacteria and tumours: Causative agents or opportunistic inhabitants? Infect. Agent. Cancer 8, 11 (2013). doi: 10.1186/1750-9378-8-11 pmid:23537317 23537317 PMC3668256 source

      Not checked in the free run.

    • cites [62] Baban CK, Cronin M, O’Hanlon D, O’Sullivan GC, Tangney M, Bacteria as vectors for gene therapy of cancer. Bioeng. Bugs 1, 385– 394 (2010). doi: 10.4161/bbug.1.6.13146 pmid:21468205 21468205 PMC3056088 source

      Not checked in the free run.

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

    Premisecitation

    Arsenic is a Group 1 carcinogen that can increase breast cancer risk and has been shown to induce estrogen receptor expression in human breast cancer.

    “Arsenic is a Group 1 carcinogen that can increase the risk of breast cancer (54) and has been shown to induce expression of the estrogen receptor in human breast cancer (55).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [54] Khanjani N, Jafarnejad A-B, Tavakkoli L, Arsenic and breast cancer: A systematic review of epidemiologic studies. Rev. Environ. Health 32, 267– 277 (2017). doi: 10.1515/reveh-2016-0068 pmid:28284039 28284039 source

      Not checked in the free run.

    • cites [55] Du J, Zhou N, Liu H, Jiang F, Wang Y, Hu C, Qi H, Zhong C, Wang X, Li Z, Arsenic induces functional re-expression of estrogen receptor α by demethylation of DNA in estrogen receptor-negative human breast cancer. PLOS ONE 7, e35957 (2012). doi: 10.1371/journal.pone.0035957pmid:22558281 22558281 PMC3338760 source

      Not checked in the free run.

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

    Premisecitation

    Bacteria may find shelter in the immunosuppressed conditions of tumors.

    “As tumors develop, their disorganized, leaky vasculature may allow circulating bacteria to enter, and the immunosuppressed environment may provide a refuge for them (61, 62).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [61] Cummins J, Tangney M, Bacteria and tumours: Causative agents or opportunistic inhabitants? Infect. Agent. Cancer 8, 11 (2013). doi: 10.1186/1750-9378-8-11 pmid:23537317 23537317 PMC3668256 source

      Not checked in the free run.

    • cites [62] Baban CK, Cronin M, O’Hanlon D, O’Sullivan GC, Tangney M, Bacteria as vectors for gene therapy of cancer. Bioeng. Bugs 1, 385– 394 (2010). doi: 10.4161/bbug.1.6.13146 pmid:21468205 21468205 PMC3056088 source

      Not checked in the free run.

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

    Premisecitation

    A previous study that reanalyzed TCGA genomic and transcriptomic data for microbial sequences reported links between cancer types and particular microbiota.

    “This is consistent with a recent publication that demonstrated that reexamination of whole-genome and whole-transcriptome sequencing data from The Cancer Genome Atlas (TCGA) for microbial sequences identified associations between different cancer types and specific microbiota (19).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] Poore GD, Kopylova E, Zhu Q, Carpenter C, Fraraccio S, Wandro S, Kosciolek T, Janssen S, Metcalf J, Song SJ, Kanbar J, Miller-Montgomery S, Heaton R, Mckay R, Patel SP, Swafford AD, Knight R, Microbiome analyses of blood and tissues suggest cancer diagnostic approach. Nature 579, 567– 574 (2020). doi: 10.1038/s41586-020-2095-1pmid:32214244 32214244 PMC7500457 source

      Not checked in the free run.

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

    Interpretationown data

    The tumor functional enrichment pattern resembles the greater stability of functions than of taxa seen in the human gut microbiome.

    “This observation is somewhat analogous to the relative stability of the human gut microbiome functions compared with its microbial taxa (58, 59).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [58] Human Microbiome Project Consortium, Structure, function and diversity of the healthy human microbiome. Nature 486, 207– 214 (2012). doi: 10.1038/nature11234 pmid:22699609 22699609 PMC3564958 source

      Not checked in the free run.

    • cites [59] Eng A, Borenstein E, Taxa-function robustness in microbial communities. Microbiome 6, 45 (2018).doi: 10.1186/s40168-018-0425-4pmid:29499759 29499759 PMC5833107 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    High levels of cigarette smoke metabolites in lung tumors may create a preferred niche for bacteria that can use these metabolites.

    “The enrichment for bacteria with the predicted capability to degrade cigarette smoke metabolites in lung tumors may suggest that high levels of these metabolites create a preferred niche for bacteria that can use these metabolites.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Predicted MetaCyc pathways from 16S sequences accurately represent the functional capabilities of intratumor bacteria.
38 of 38

  • The paper relies on this without support.

    Predicted MetaCyc pathways from 16S sequences accurately represent the functional capabilities of intratumor bacteria.

    “we used the PICRUSt2 tool (50-52) to map the 16S sequences to the genes and pathways that these bacterial species may harbor”

  • The paper relies on this without support.

    Patients' smoking status was accurately recorded.

    “we compared the bacterial functions found in non–small cell lung cancers (NSCLCs) of 100 current smokers with those in NSCLCs of 43 people who had never smoked (never-smokers).”

  • The paper relies on this without support.

    The classification of melanoma patients as responders or nonresponders to immune checkpoint inhibitors is accurate.

    “we compared metastatic melanomas from patients who responded to immune checkpoint inhibitors (ICI) (n = 29) with those from patients who did not respond (n = 48).”

  • The paper relies on this without support.

    Breast cancer subtype assignment by ER, PR, and HER2 status is accurate.

    “when comparing different subtypes of breast cancer according to their estrogen receptor (ER), progesterone receptor (PR), and HER2 status”
4 of 4

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?

  • Many breast cancer GOMS components had previously been identified in an analysis of breast cancer microbiome comprising more than 9,000 species after filtering artefactual contaminants.

    “many of these breast cancer GOMS components (V. parvula, B. uniformis and E. clostridioformis, among others) had previously been identified in an analysis of the breast cancer microbiome comprising >9,000 species after filtering for artefactual contaminants69.”

    From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [69]

  • Multiple bacterial taxa differed significantly between responders and non-responders, with Veillonellaceae and Gammaproteobacteria associated with resistance, as previously identified in GOMS.

    “While the overall bacterial load was similar in responders and non-responders, multiple bacterial taxa had significantly different representation, notably Veillonellaceae and Gammaproteobacteria were associated with resistance, as already identified in GOMS.”

    From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [69]

  • In a metastatic melanoma cohort of 29 responders and 48 non-responders, overall bacterial load was similar between responders and non-responders.

    “While the overall bacterial load was similar in responders and non-responders, multiple bacterial taxa had significantly different representation, notably Veillonellaceae and Gammaproteobacteria were associated with resistance, as already identified in GOMS.”

    From Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy (2023) · cites this paper as [69]

  • Across cancer indications and geographic sites, the taxonomic composition of gut and to some degree tumor microbiota correlates with ICI responses in melanoma and other cancers.

    “First, correlations have been drawn across cancer indications and geographical sites between the taxonomic composition of the gut (and to some degree tumor) microbiota, and ICI responses in patients with melanoma and other cancers.”

    From Melanoma and microbiota: Current understanding and future directions (2024) · cites this paper as [14]

  • Quantitative PCR estimated that among seven cancer types approximately 0.68% (95% CI: 0.75, 1.46%) of tumor cellular content is bacterial, with melanoma-specific density estimates at about 33 bacteria/mm2 or 6.3×10^6 bacteria/cm3 on average.

    “Quantitative PCR has estimated that among seven cancer types, approximately 0.68% (95% CI: 0.75, 1.46%) of the tumor cellular content is bacterial, with melanoma-specific density estimates at ~33 bacteria/mm2 or ~6.3×106 bacteria/cm3 on average (using bootstrapped values).”

    From Melanoma and microbiota: Current understanding and future directions (2024) · cites this paper as [14]

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.

  • Conflicting statements about LTA in cancer cells

    Minor

    One passage says LTA was rarely detected in cancer cells, which implies some detections. A later passage says none was detected there.

1 of 1

Cites

1 retracted

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Nejman, D., Livyatan, I., Fuks, G., Gavert, N., Zwang, Y., Geller, L. T., Rotter-Maskowitz, A., Weiser, R., Mallel, G., Gigi, E., Meltser, A., Douglas, G. M., Kamer, I., Gopalakrishnan, V., Dadosh, T., Levin-Zaidman, S., Avnet, S., Atlan, T., Cooper, Z. A., Arora, R., Cogdill, A. P., Khan, M. A. W., Ologun, G., Bussi, Y., Weinberger, A., Lotan-Pompan, M., Golani, O., Perry, G., Rokah, M., Bahar-Shany, K., Rozeman, E. A., Blank, C. U., Ronai, A., Shaoul, R., Amit, A., Dorfman, T., Kremer, R., Cohen, Z. R., Harnof, S., Siegal, T., Yehuda-Shnaidman, E., Gal-Yam, E. N., Shapira, H., Baldini, N., Langille, M. G. I., Ben-Nun, A., Kaufman, B., Nissan, A., Golan, T., Dadiani, M., Levanon, K., Bar, J., Yust-Katz, S., Barshack, I., Peeper, D. S., Raz, D. J., Segal, E., Wargo, J. A., Sandbank, J., Shental, N., & Straussman, R.
Affiliations
  • Weizmann Institute of Science (IL)
  • Tel Aviv University (IL)
  • Dalhousie University (CA)
  • Sheba Medical Center (IL)
  • The University of Texas MD Anderson Cancer Center (US)
  • Department of Chemical Research Support, Weizmann Institute of Science, Rehovot, Israel.
  • Istituto Ortopedico Rizzoli (IT)
  • Jerusalem College of Technology (IL)
  • AstraZeneca (United States) (US)
  • Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
  • Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel.
  • The Netherlands Cancer Institute (NL)
  • Rambam Health Care Campus (IL)
  • Technion – Israel Institute of Technology (IL)
  • Rabin Medical Center (IL)
  • Institute of Pathology, Megalab, Maccabi Healthcare Services, Rehovot, Israel.
  • Breast Oncology Institute, Sheba Medical Center, Ramat Gan, Israel.
  • Maccabi Healthcare Services (IL)
  • Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
  • City Of Hope National Medical Center (US)
  • Open University of Israel (IL)
Corresponding author
  • Nejman, Deborah
  • Livyatan, Ilana
  • Fuks, Garold
  • Shental, Noam
  • Straussman, Ravid
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2020-05-29
Volume
368
Issue
6494
Pages
973-980
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.aay9189
PMC
PMC7757858
OpenAlex
W3030942202
Cited by
2,464
References
73
Citations by year
2026: 425 · 2025: 524 · 2024: 466 · 2023: 415 · 2022: 335 · 2021: 234 · 2020: 63
FWCI
85.73
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, other-oa)
Funders
  • National Institutes of Health (1R01CA219896-01A1)
  • American Association for Cancer Research (SU2C-AACR-IRG-19-17)
  • Israel Cancer Research Fund
  • H2020 European Research Council (818086)
  • United States-Israel Binational Science Foundation (2013332)
  • Israel Ministry of Science, Technology & Space (3-11174)
  • Israel Science Foundation (2044/17)
  • Rising Tide Foundation
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Keywords
tumor microbiome, intratumoral bacteria, intracellular bacteria, breast cancer, lung cancer, ovarian cancer, pancreatic cancer, melanoma, bone tumors, brain tumors, tumor subtypes, smoking, immunotherapy response, tumor immune cells
MeSH terms
Bacteria, Breast, Colon, Female, Humans, Immunotherapy, Lung, Macrophages, Male, Neoplasms, Ovary, RNA, Ribosomal, 16S, Microbiota

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 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

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.

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