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2.
iScience ; 27(6): 110157, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38952680

ABSTRACT

Fusobacterium nucleatum is an oral commensal bacterium that can colonize extraoral tumor entities, such as colorectal cancer and breast cancer. Recent studies revealed its ability to modulate the immune response in the tumor microenvironment (TME), promoting cancer progression and metastasis. Importantly, F. nucleatum subsp. animalis was shown to bind to Siglec-7 via lipopolysaccharides, leading to a pro-inflammatory profile in human monocyte-derived dendritic cells. In this study, we show that F. nucleatum subsp. nucleatum RadD binds to Siglec-7 on NK cells, thereby inhibiting NK cell-mediated cancer cell killing. We demonstrate that this binding is dependent on arginine residue R124 in Siglec-7. Finally, we determine that this binding is independent of the known interaction of RadD with IgA. Taken together, our findings elucidate the targeting of Siglec-7 by F. nucleatum subsp. nucleatum RadD as a means to modulate the NK cell response and potentially promoting immune evasion and tumor progression.

3.
PLoS Pathog ; 20(1): e1011923, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38215172

ABSTRACT

Natural killer cells (NKs) found during pregnancy at the maternal-fetal interface named decidual (d)NKs, show signs of education following first pregnancy, resulting in better placentation and fetus-growth, hence termed pregnancy trained dNKs (PTdNKs). Here we show that PTdNKs provide increased protection of the fetus from Fusobacterium nucleatum (FN) infection. We demonstrate that PTdNKs secrete elevated amounts of the bacteriocidal protein granulysin (GNLY) upon incubation with FN compared to dNKs derived from first pregnancies, which leads to increased killing of FN. Furthermore, we showed mechanistically that the GNLY secretion is mediated through the interaction of the FN's Fap2 protein with Gal-GalNAc present on PTdNKs. Finally, we show in vivo, using GNLY-tg mice that enhanced protection of the fetuses from FN infection is observed, as compared to wild type and that this enhance protection is NK cell dependent. Altogether, we show a new function for PTdNKs as protectors of the fetus from bacterial infection.


Subject(s)
Decidua , Fusobacterium nucleatum , Pregnancy , Female , Mice , Animals , Decidua/metabolism , Killer Cells, Natural/metabolism
4.
Bio Protoc ; 13(6): e4635, 2023 Mar 20.
Article in English | MEDLINE | ID: mdl-36968439

ABSTRACT

Over the past decades, the main techniques used to visualize bacteria in tissue have improved but are still mainly based on indirect recognition of bacteria. Both microscopy and molecular recognition are being improved, but most procedures for bacteria detection in tissue involve extensive damage. Here, we describe a method to visualize bacteria in tissue slices from an in vivo model of breast cancer. This method allows examining trafficking and colonization of fluorescein-5-isothiocyanate (FITC)-stained bacteria in various tissues. The protocol provides direct visualization of fusobacterial colonization in breast cancer tissue. Rather than processing the tissue or confirming bacterial colonization by PCR or culture, the tissue is directly imaged using multiphoton microscopy. This direct visualization protocol causes no damage to the tissue; therefore, all structures can be identified. This method can be combined with others to co-visualize bacteria, types of cells, or protein expression in cells.

5.
Front Cell Infect Microbiol ; 12: 968739, 2022.
Article in English | MEDLINE | ID: mdl-36118038

ABSTRACT

Bladder cancer is the 4th leading cancer in men. Tumor resection followed by bladder instillation of Bacillus Calmette-Guérin (BCG) is the primary treatment for high-risk patients with Non-Muscle Invasive Bladder Cancer (NMIBC) to prevent recurrence and progression to muscle-invasive disease. This treatment, however, lacks efficiency and causes severe adverse effects. Mannose residues are expressed on bladder surfaces and their levels were indicated to be higher in bladder cancer. Intravesical instillations of a recombinant Pseudomonas aeruginosa (PA) overexpressing the mannose-sensitive hemagglutination fimbriae (PA-MSHA), and of a mannose-specific lectin-drug conjugate showed efficiency against NMIBC in murine models of bladder cancer. Urothelial mannosylation facilitates bladder colonization by Uropathogenic E. coli (UPEC) via the interaction with the FimH mannose lectin, positioned at the tip of type 1 fimbria. A recombinant BCG strain overexpressing FimH on its outer surface, exhibited higher attachment and internalization to bladder cancer cells and increased effectivity in treating bladder cancer in mice. Investigating the pattern of mannose expression in NMIBC is important for improving treatment. Here, using tissue microarrays containing multiple normal and cancerous bladder samples, and lectins, we confirm that human bladder cancer cells express high mannose levels. Using UPEC mutants lacking or overexpressing type 1 fimbria, we also demonstrate that tumor-induced hypermannosylation increases type 1 fimbria mediated UPEC attachment to human and mouse bladder cancer. Our results provide an explanation for the effectiveness of PA-MSHA and the FimH-overexpressing BCG and support the hypothesis that mannose-targeted therapy holds potential for improving bladder cancer treatment.


Subject(s)
Mycobacterium bovis , Urinary Bladder Neoplasms , Uropathogenic Escherichia coli , Animals , BCG Vaccine , Fimbriae Proteins/metabolism , Humans , Lectins , Mannose , Mannose-Binding Lectins , Mice , Pseudomonas aeruginosa/metabolism , Urinary Bladder Neoplasms/pathology , Uropathogenic Escherichia coli/genetics , Uropathogenic Escherichia coli/metabolism
6.
Biomolecules ; 12(9)2022 09 07.
Article in English | MEDLINE | ID: mdl-36139097

ABSTRACT

Intestinal bacterial communities participate in gut homeostasis and are recognized as crucial in bowel inflammation and colorectal cancer (CRC). Fusobacterium nucleatum (Fn), a pathobiont of the oral microflora, has recently emerged as a CRC-associated microbe linked to disease progression, metastasis, and a poor clinical outcome; however, the primary cellular and/or microenvironmental targets of this agent remain elusive. We report here that Fn directly targets putative colorectal cancer stem cells (CR-CSCs), a tumor cell subset endowed with cancer re-initiating capacity after surgery and chemotherapy. A patient-derived CSC line, highly enriched (70%) for the stem marker CD133, was expanded as tumor spheroids, dissociated, and exposed in vitro to varying amounts (range 100-500 MOI) of Fn. We found that Fn stably adheres to CSCs, likely by multiple interactions involving the tumor-associated Gal-GalNac disaccharide and the Fn-docking protein CEA-family cell adhesion molecule 1 (CEACAM-1), robustly expressed on CSCs. Importantly, Fn elicited innate immune responses in CSCs and triggered a growth factor-like, protein tyrosine phosphorylation cascade largely dependent on CEACAM-1 and culminating in the activation of p42/44 MAP kinase. Thus, the direct stimulation of CSCs by Fn may contribute to microbiota-driven colorectal carcinogenesis and represent a target for innovative therapies.


Subject(s)
Colorectal Neoplasms , Fusobacterium Infections , Neoplastic Stem Cells , Antigens, CD , Cell Adhesion Molecules , Colorectal Neoplasms/pathology , Disaccharides , Fusobacterium Infections/complications , Fusobacterium Infections/microbiology , Fusobacterium nucleatum/physiology , Humans , Neoplastic Stem Cells/metabolism , Tyrosine
7.
Nat Commun ; 13(1): 2463, 2022 05 05.
Article in English | MEDLINE | ID: mdl-35513379

ABSTRACT

Candida albicans is the most common fungal pathogen and a prevalent cause of deadly bloodstream infections. Better understanding of the immune response against it, and the ways by which it evades immunity, are crucial for developing new therapeutics against it. Natural Killer (NK) cells are innate lymphocytes best known for their role against viruses and tumors. In recent years it became clear that NK cells also play an important role in anti-fungal immunity. Here we show that while NK cells recognize and eliminate C. albicans, the fungal cells inhibit NK cells by manipulating the immune checkpoint receptor TIGIT (T cell immunoreceptor with Ig and ITIM domains) in both humans and mice. We identify the responsible fungal ligands as members of the Als (Agglutinin-Like Sequences) protein family. Furthermore, we show that blocking this interaction using immunotherapy with a TIGIT-blocking antibody can re-establish anti-Candida immunity and serve as a potential therapeutic tool.


Subject(s)
Agglutinins , Candida albicans , Agglutinins/metabolism , Animals , Candida albicans/metabolism , Immunotherapy , Killer Cells, Natural , Mice , Receptors, Immunologic/metabolism
8.
Periodontol 2000 ; 89(1): 166-180, 2022 06.
Article in English | MEDLINE | ID: mdl-35244982

ABSTRACT

Accumulating evidence demonstrates that the oral pathobiont Fusobacterium nucleatum is involved in the progression of an increasing number of tumors types. Thus far, the mechanisms underlying tumor exacerbation by F. nucleatum include the enhancement of proliferation, establishment of a tumor-promoting immune environment, induction of chemoresistance, and the activation of immune checkpoints. This review focuses on the mechanisms that mediate tumor-specific colonization by fusobacteria. Elucidating the mechanisms mediating fusobacterial tumor tropism and promotion might provide new insights for the development of novel approaches for tumor detection and treatment.


Subject(s)
Fusobacterium Infections , Neoplasms , Fusobacterium Infections/microbiology , Fusobacterium nucleatum/physiology , Humans
9.
Cell Rep ; 38(12): 110537, 2022 03 22.
Article in English | MEDLINE | ID: mdl-35320712

ABSTRACT

While the existence of an indigenous placental microbiota remains controversial, several pathogens are known to be involved in adverse pregnancy outcomes. Fusobacterium nucleatum is an oral bacterium that is one of several bacteria associated with preterm birth. Oral fusobacteria translocate to the placenta hematogenously; however, the mechanisms localizing them to the placenta remain unclear. Here, using peanut agglutinin, we demonstrate that the level of Gal-GalNAc (Galß1-3GalNAc; Thomsen Friedenreich antigen) found on trophoblasts facing entering maternal blood rises during gestation and is recognized by the fusobacterial Fap2 Gal-GalNAc lectin. F. nucleatum binding to human and mouse placenta correlates with Gal-GalNAc levels and is reduced upon O-glycanase treatment or with soluble Gal-GalNAc. Fap2-inactivated F. nucleatum shows reduced binding to Gal-GalNAc-displaying placental sections. In a mouse model, intravenously injected Fap2-expressing F. nucleatum, but not a Fap2 mutant, reduces mouse fetal survival by 70%.


Subject(s)
Fusobacterium nucleatum , Premature Birth , Adenomatous Polyposis Coli , Animals , Antigens, Tumor-Associated, Carbohydrate , Female , Lectins , Mice , Placenta , Pregnancy
10.
Front Cell Infect Microbiol ; 11: 699015, 2021.
Article in English | MEDLINE | ID: mdl-34395310

ABSTRACT

Recent studies on the oral, anaerobic, gram-negative bacterium Fusobacterium nucleatum revealed its presence and involvement in colorectal, esophageal and breast cancer. We previously demonstrated that F. nucleatum binds and activates the human inhibitory receptors TIGIT and CEACAM1 leading to inhibition of T and NK cell anti-tumor immunity. CEACAM1 was found to be bound and activated by the fusobacterial trimeric autotransporter adhesin CbpF. Here we report the generation of a recombinant E. coli expressing full-length CbpF that efficiently binds and activates CEACAM1.


Subject(s)
Escherichia coli , Fusobacterium nucleatum , Antigens, CD , Cell Adhesion Molecules/genetics , Escherichia coli/genetics , Humans , Type V Secretion Systems
11.
Front Cell Infect Microbiol ; 11: 692544, 2021.
Article in English | MEDLINE | ID: mdl-34336716

ABSTRACT

F. nucleatum is an anaerobic bacterium that is associated with several tumor entities and promotes tumorigenesis. Recent evidence suggests that F. nucleatum binds the inhibitory receptor carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) via the trimeric autotransporter adhesin CbpF. However, whether this binding is functional or whether other fusobacterial trimeric autotransporter adhesins are involved in CEACAM1 activation is unknown. In this study, using F. nucleatum mutants lacking the type 5c trimeric autotransporter adhesins fvcA (CbpF), fvcB, fvcC, and fvcD, we show that F. nucleatum CbpF binds and activates CEACAM1 and also binds carcinoembryonic antigen (CEA), a tumor-associated protein. We further find that CEACAM antibodies directed against the CEACAM N-terminal domain block the CbpF-CEACAM1 interaction. In functional assays, we demonstrate CbpF-dependent inhibition of CD4+ T cell response. Thus, we characterize an immune evasion mechanism in which F. nucleatum uses its surface protein CbpF to inhibit T cell function by activating CEACAM1.


Subject(s)
Cell Adhesion Molecule-1/immunology , Fusobacterium Infections/immunology , Immune Evasion , T-Lymphocytes , Fusobacterium nucleatum , Humans , T-Lymphocytes/immunology , T-Lymphocytes/microbiology
12.
Eur J Immunol ; 51(9): 2218-2224, 2021 09.
Article in English | MEDLINE | ID: mdl-34268737

ABSTRACT

Neutrophils play a crucial role in immune defense against and clearance of uropathogenic Escherichia coli (UPEC)-mediated urinary tract infection, the most common bacterial infection in healthy humans. CD300a is an inhibitory receptor that binds phosphatidylserine and phosphatidylethanolamine, presented on the membranes of apoptotic cells. CD300a binding to phosphatidylserine and phosphatidylethanolamine, also known as the "eat me" signal, mediates immune tolerance to dying cells. Here, we demonstrate for the first time that CD300a plays an important role in the neutrophil-mediated immune response to UPEC-induced urinary tract infection. We show that CD300a-deficient neutrophils have impaired phagocytic abilities and despite their increased accumulation at the site of infection, they are unable to reduce bacterial burden in the bladder, which results in significant exacerbation of infection and worse host outcome. Finally, we demonstrate that UPEC's pore forming toxin α-hemolysin induces upregulation of the CD300a ligand on infected bladder epithelial cells, signaling to neutrophils to be cleared.


Subject(s)
Escherichia coli Infections/prevention & control , Neutrophils/immunology , Receptors, Immunologic/deficiency , Receptors, Immunologic/immunology , Urinary Tract Infections/immunology , Uropathogenic Escherichia coli/immunology , Animals , Apoptosis/immunology , Escherichia coli Infections/immunology , Escherichia coli Proteins/metabolism , Female , Gene Knockout Techniques , Hemolysin Proteins/metabolism , Mice , Mice, Inbred BALB C , Phagocytosis/genetics , Phagocytosis/immunology , Phosphatidylethanolamines/metabolism , Phosphatidylserines/metabolism , Receptors, Immunologic/genetics , Urinary Bladder/immunology , Urinary Bladder/microbiology , Urinary Bladder/pathology , Urinary Tract Infections/microbiology , Uropathogenic Escherichia coli/growth & development
13.
FEMS Microbiol Rev ; 45(5)2021 09 08.
Article in English | MEDLINE | ID: mdl-33765142

ABSTRACT

Some cancer treatment failures have been attributed to the tumour microbiota, with implications that microbiota manipulation may improve treatment efficacy. While antibiotics have been used to control bacterial growth, their dysbiotic effects on the microbiome, failure to penetrate biofilms and decreased efficacy due to increasing antimicrobial resistance by bacteria, suggest alternatives are needed. Bacteriophages may provide a precise means for targeting oncobacteria whose relative abundance is increased in tumour tissue microbiomes. Fusobacterium, Streptococcus, Peptostreptococcus, Prevotella, Parvimonas, and Treponema species are prevalent in tumour tissue microbiomes of some cancers. They may promote cancer growth by dampening immunity, stimulating release of proinflammatory cytokines, and directly interacting with cancer cells to stimulate proliferation. Lytic bacteriophages against some of these oncobacteria have been isolated and characterised. The search continues for others. The possibility exists for their testing as adjuncts to complement existing therapies. In this review, we highlight the role of oncobacteria, specifically those whose relative abundance in the intra-tumour microbiome is increased, and discuss the potential for bacteriophages against these micro-organisms to augment existing cancer therapies. The capacity for bacteriophages to modulate immunity and kill specific bacteria makes them suitable candidates to manipulate the tumour microbiome and negate the effects of these oncobacteria.


Subject(s)
Bacteriophages , Microbiota , Neoplasms , Dysbiosis , Humans , Neoplasms/therapy , Tumor Microenvironment
14.
Cell Rep ; 34(9): 108766, 2021 03 02.
Article in English | MEDLINE | ID: mdl-33657368

ABSTRACT

Group A Streptococcus (GAS) causes diverse human diseases, including life-threatening soft-tissue infections. It is accepted that the human antimicrobial peptide LL-37 protects the host by killing GAS. Here, we show that GAS extracellular protease ScpC N-terminally cleaves LL-37 into two fragments of 8 and 29 amino acids, preserving its bactericidal activity. At sub-bactericidal concentrations, the cleavage inhibits LL-37-mediated neutrophil chemotaxis, shortens neutrophil lifespan, and eliminates P2X7 and EGF receptors' activation. Mutations at the LL-37 cleavage site protect the peptide from ScpC-mediated splitting, maintaining all its functions. The mouse LL-37 ortholog CRAMP is neither cleaved by ScpC nor does it activate P2X7 or EGF receptors. Treating wild-type or CRAMP-null mice with sub-bactericidal concentrations of the non-cleavable LL-37 analogs promotes GAS clearance that is abolished by the administration of either P2X7 or EGF receptor antagonists. We demonstrate that LL-37-mediated activation of host receptors is critical for defense against GAS soft-tissue infections.


Subject(s)
Antimicrobial Cationic Peptides/metabolism , ErbB Receptors/metabolism , Neutrophils/microbiology , Receptors, Purinergic P2X7/metabolism , Streptococcal Infections/microbiology , Streptococcus pyogenes/pathogenicity , Animals , Anti-Bacterial Agents/pharmacology , Antimicrobial Cationic Peptides/pharmacology , Bacterial Proteins/metabolism , Cathelicidins/genetics , Cathelicidins/metabolism , Cell Line , Disease Models, Animal , Female , Host-Pathogen Interactions , Humans , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Neutrophils/drug effects , Neutrophils/metabolism , Serine Endopeptidases/metabolism , Signal Transduction , Streptococcal Infections/drug therapy , Streptococcal Infections/genetics , Streptococcal Infections/metabolism , Streptococcus pyogenes/enzymology , Streptococcus pyogenes/genetics , Substrate Specificity
15.
Article in English | MEDLINE | ID: mdl-32850497

ABSTRACT

Fusobacterium nucleatum is a common oral bacterium that is enriched in colorectal adenomas and adenocarcinomas (CRC). In humans, high fusobacterial CRC abundance is associated with chemoresistance and poor prognosis. In animal models, fusobacteria accelerate CRC progression. Targeting F. nucleatum may reduce fusobacteria cancer progression and therefore determining the origin of CRC F. nucleatum and the route by which it reaches colon tumors is of biologic and therapeutic importance. Arbitrarily primed PCR performed previously on matched same-patients CRC and saliva F. nucleatum isolates, suggested that CRC F. nucleatum may originate from the oral cavity. However, the origin of CRC fusobacteria as well as the route of their arrival to the tumor have not been well-established. Herein, we performed and analyzed whole genome sequencing of paired, same-patient oral, and CRC F. nucleatum isolates and confirmed that CRC-fusobacteria originate from the oral microbial reservoir. Oral fusobacteria may translocate to CRC by descending via the digestive tract or using the hematogenous route during frequent transient bacteremia caused by chewing, daily hygiene activities, or dental procedures. Using the orthotropic CT26 mouse model we previously showed that IV injected F. nucleatum colonize CRC. Here, we compared CRC colonization by gavage vs. intravenous inoculated F. nucleatum in the MC38 and CT26 mouse orthotropic CRC models. Under the tested conditions, hematogenous fusobacteria were more successful in CRC colonization than gavaged ones. Our results therefore provide evidence that the hematogenous route may be the preferred way by which oral fusobacteria reach colon tumors.


Subject(s)
Cardiovascular System , Colonic Neoplasms , Fusobacterium Infections , Animals , Fusobacterium nucleatum , Humans , Mouth
16.
Nat Commun ; 11(1): 3259, 2020 06 26.
Article in English | MEDLINE | ID: mdl-32591509

ABSTRACT

Fusobacterium nucleatum is an oral anaerobe recently found to be prevalent in human colorectal cancer (CRC) where it is associated with poor treatment outcome. In mice, hematogenous F. nucleatum can colonize CRC tissue using its lectin Fap2, which attaches to tumor-displayed Gal-GalNAc. Here, we show that Gal-GalNAc levels increase as human breast cancer progresses, and that occurrence of F. nucleatum gDNA in breast cancer samples correlates with high Gal-GalNAc levels. We demonstrate Fap2-dependent binding of the bacterium to breast cancer samples, which is inhibited by GalNAc. Intravascularly inoculated Fap2-expressing F. nucleatum ATCC 23726 specifically colonize mice mammary tumors, whereas Fap2-deficient bacteria are impaired in tumor colonization. Inoculation with F. nucleatum suppresses accumulation of tumor infiltrating T cells and promotes tumor growth and metastatic progression, the latter two of which can be counteracted by antibiotic treatment. Thus, targeting F. nucleatum or Fap2 might be beneficial during treatment of breast cancer.


Subject(s)
Breast Neoplasms/microbiology , Breast Neoplasms/pathology , Disease Progression , Fusobacterium nucleatum/growth & development , Animals , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/metabolism , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/immunology , Cell Line, Tumor , Cell Proliferation/drug effects , Colony Count, Microbial , DNA, Bacterial/genetics , Disease Models, Animal , Female , Fusobacterium nucleatum/drug effects , Fusobacterium nucleatum/genetics , Galactosamine/metabolism , Galactose/metabolism , Genome, Bacterial/genetics , Humans , Immunity/drug effects , Lung Neoplasms/secondary , Mice, Inbred BALB C , Neoplasm Metastasis
17.
Oncoimmunology ; 8(6): e1581531, 2019.
Article in English | MEDLINE | ID: mdl-31069151

ABSTRACT

Fusobacterium nucleatum (F. nucleatum) is an oral anaerobe found to be enriched in colorectal cancer (CRC). Presence of F. nucleatum in CRC has been correlated with resistance to chemotherapy and poor prognosis. We previously demonstrated that the Fap2 outer-surface protein of F. nucleatum binds and activates the human inhibitory receptor TIGIT which is expressed by T and Natural Killer (NK) cells, and inhibits anti-tumor immunity. Here we show that F. nucleatum also binds and activates the human inhibitory receptor CEACAM1 leading to inhibition of T and NK cells activities. Our results suggest that using CEACAM1 and TIGIT inhibitors and specific targeting of fusobacteria should be considered for treating fusobacteria-colonized tumors.

18.
Oncoimmunology ; 8(4): e1553487, 2019.
Article in English | MEDLINE | ID: mdl-30906650

ABSTRACT

We previously showed that the colorectal cancer colonizing bacterium Fusobacterium nucleatum protects tumors from immune cell attack via binding of the fusbacterial Fap2 outer-membrane protein to TIGIT, a checkpoint inhibitory receptor expressed on T cells and NK cells. Helicobacter pylori, the causative agent for peptic ulcer disease, is associated with the development of gastric adenocarcinoma and MALT lymphoma. The HopQ outer-membrane adhesin of H. pylori was recently shown to bind carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) including CEACAM1, an inhibitory receptor expressed mainly by activated T and NK cells. Here we investigated the possibility that similar to Fap2, HopQ can also inhibit immune cell activities by interacting with CEACAM1. We used several approaches to confirm that HopQ indeed interacts with CEACAM1, and show that CEACAM1-mediated activation by HopQ, may inhibit NK and T cell functions.

19.
Bio Protoc ; 8(5)2018 Mar 05.
Article in English | MEDLINE | ID: mdl-29623285

ABSTRACT

Here we describe a method to test bacterial adhesion to paraffin embedded tissue sections. This method allows examining binding of different bacterial strains, transfected with a fluorescent protein reporter plasmid to various tissues, to better understand different mechanisms such as colonization. This assay provides a more physiological context to bacterial binding, than would have been achieved using adhesion assays to cell lines. The sections can be imaged using fluorescent microscopy and adhesion of various bacterial strains can be quantified and tested, simultaneously.

20.
Article in English | MEDLINE | ID: mdl-28713780

ABSTRACT

Colorectal adenocarcinoma (CRC) is a common tumor with high mortality rates. Interestingly, CRC was found to be colonized by the oral anaerobic bacteria Fusobacterium nucleatum, which accelerates tumor progression and enables immune evasion. The CRC-specific colonization by fusobacteria is mediated through the recognition of tumor displayed Gal-GalNAc moieties by the fusobacterial Fap2 Gal-GalNAc lectin. Here, we show high Gal-GalNAc levels in additional adenocarcinomas including those found in the stomach, prostate, ovary, colon, uterus, pancreas, breast, lung, and esophagus. This observation coincides with recent reports that found fusobacterial DNA in some of these tumors. Given the tumorigenic role of fusobacteria and its immune evasion properties, we suggest that fusobacterial elimination might improve treatment outcome of the above tumors. Furthermore, as fusobacteria appears to specifically home-in to Gal-GalNAc-displaying tumors, it might be engineered as a platform for treating CRC and the above common, lethal, adenocarcinomas.


Subject(s)
Adenocarcinoma/microbiology , Carcinogenesis , Colonic Neoplasms/microbiology , Fusobacterium nucleatum/pathogenicity , Adenocarcinoma/pathology , Antigens, Tumor-Associated, Carbohydrate/analysis , Carcinogenesis/pathology , Colonic Neoplasms/pathology , Fusobacterium nucleatum/genetics , Fusobacterium nucleatum/immunology , Host-Pathogen Interactions , Humans , Immune Evasion , Lectins/metabolism , Liver Neoplasms/pathology , Pilot Projects , Sarcoma/pathology
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