Cancer and microbes

Identifying and combating the risk factors behind tumor development.

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At least 30% of cancers are linked to identified risk factors. More than one in six cases of cancer worldwide are caused by infection. Today, thanks to research into cancer-causing pathogens, Institut Pasteur researchers are developing new strategies for combating the cancers they cause. For example, the hepatitis B vaccine, which was developed at the Institut Pasteur, has prevented hundreds of thousands of cases of liver cancer in many countries. Developing new vaccines against cancer-causing pathogens is a major avenue for research. Furthermore, recent findings point to certain microbes or compounds of microbial origin as risk factors, whereas others appears has beneficial and would promote the efficacy of existing anti-cancer treatments such as chemotherapy or immunomodulators. Thus, researchers from Institut Pasteur study the molecular bases underlying the microbiom effects in order to identify and decrease of eliminate risk factors.

Department of Cell Biology & Infection

Jost Enninga

Jost-Enninga’s team works on the intracellular niche formation of bacterial pathogens including Salmonella and Shigella. These pathogens have been shown to crosstalk with major host cell pathways involved in cell transformation and cancer development. The scientists study why only some subpopulation of the infecting bacteria interfere with the singling events associated with cancer. It will lead to a better understanding of the links between intestinal cancer and food borne pathogens. 

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Pascal Pineau

Pascal Pineau’s team is involved in a collaborative project (IRD, INEN) on hepatocellular carcinoma in children and adolescent from Peru. In this population with Native American ancestry, massive tumors are induced in absence of concomitant liver damage despite the constant presence of a stealth hepatitis B virus infection. Mutation spectra in these tumors are different from that of other liver cancers and multi-omics analysis revealed a unique molecular signature. His team is currently searching for the risk factor(s) that together with HBV might explain this peculiar tumor presentation. In parallel, Pascal Pineau is coordinating a project with Instituts Pasteur of Iran and Morocco on the role of the gut microbiota in liver tumorigenesis.

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Agathe Subtil

Host-pathogen interactions shed light on metabolic changes occurring during tumorigenesis.

Some very peculiar bacteria, called intracellular bacteria because they multiply in a “host” cell, have developed mechanisms to modify the metabolism of this host to meet they own needs. The project of this unit is based on the concept that some of these modifications are identical to those that occur during tumorigenesis, this time not to sustain bacterial growth but to feed the fast proliferation of cancer cells. They have recently proven this concept with the study of the activity of a human enzyme activated in many cancers, called transglutaminase 2. This research axis is being continued by the comparison of the consequences of the activation of transglutaminase 2 in cells infected with Chlamydia trachomatis and in ovarian cancer cells.

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Department of Immunology

Gérard Eberl

Regulation of susceptibility to cancer by early life microbiota

The colonization of the intestine by the microbiota elicits a vigorous immune response termed the weaning reaction. This weaning reaction regulates the reactivity of the immune system and the susceptibility to inflammatory pathology later in life. In the absence of microbiota at weaning, excessive inflammation develops in the adult that significantly increase the incidence of colorectal cancer. This unit is now investigating the mechanisms that lead to excessive inflammation, and develop tools to inhibit the deregulation of the immune system and its consequences on cancer development.

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Department of Microbiology

Emmanuel Lemichez

Toxines Bactériennes et cancer. Définir l'implication de profils toxiniques du microbiome dans l'évolution péjorative des tumeurs coliques en vue d'établir des stratégies prophylactiques et définir des approches thérapeutiques ciblées représente un formidable enjeu en santé publique.

L’équipe d’Emmanuel Lemichez étudie en particulier les toxines bactériennes activatrices des GTPases pro-oncogéniques Rho, comprenant le facteur CNF1 produit par certaines souches d'E. coli. Ils ont montré que CNF1 catalyse une réaction spécifique de déamidation, c’est à dire réalisant la mutation d'une glutamine clé des GTPases Rho en acide glutamique, leur conférant un gain de fonction pro-oncogénique (Flatau 1997 Nature). Ils ont montré que les formes sur-activées des petites GTPases Rho sont normalement dégradées par le système ubiquitination protéasome, une régulation fréquemment perdue dans les cellules cancéreuses (Doye 2002 Cell; Torrino 2011 Dev Cell; Zhang 2016 Mol Cell). L'étude dans le contexte de l'étiologie du cancer colorectal de ces déamidases, largement répandues dans les génomes de protéobactéries, couplée à celle des E3 ligases contrôlant la dégradation des GTPases doit permettre d’identifier de nouveaux suppresseurs de tumeur et de mieux comprendre l'incidence élevée des cancer colorectaux dans les pays industrialisés pour lesquels on observe une forte prévalence de souches pathogènes d'E. coli.

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Eliette Touati

Helicobacter pylori infection and gastric cancer

Their projects are focused on the relationships between infection and cancer, using as a model system Helicobacter pylori infection and gastric cancer. They include both fundamental and clinical aspects. Their objectives are to characterize the early events responsible for the initiation/promotion of gastric carcinogenesis during H. pylori infection. The mechanisms at the origin of genetic instabilities and epigenetic deregulation in host cells and their consequences on the genotoxic/oncogenic activities of the infection are particularly focused. In parallel, translational approaches are developed with clinicians to identify biomarker candidates in blood for an early detection/prevention of gastric cancer.

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Patrick Trieu-Cuot / Shaynoor Dramsi

This team proposes a research project based on a clinically relevant bacterial model, Streptococcus gallolyticus (previously named S. bovis biotype I), an emerging cause of septicemia and infective endocarditis in the elderly, and whose presence has been strongly linked to colorectal cancer by epidemiological studies for nearly forty years.

They recently showed that colorectal cancer specific conditions promote S. gallolyticus gut colonization by a 1,000- fold in the Notch/APC mice and this competitive advantage occurs at the expense of enterococci, a common member of the gut microbiota (Aymeric et al., 2018). They recently obtained promising data indicating that S. gallolyticus can accelerate the development of intestinal tumors in the APC Min mice (Pasquereau et al., unpublished). They are currently investigating possible mechanisms through transcriptomic and histological analyses. Mechanisms sustaining bacteria-induced oncogenesis include the alteration of normal host responses such as inflammation, apoptosis and cellular proliferation. Alternatively, bacteria may also promote cancer through the production of secondary metabolites, such as reactive oxygen intermediates, or direct effect on cell transformation through the production of oncogenic toxins (e.g. CDT, colibactin, BFT).

See the website of the Biology of Gram-Positive Pathogens Unit

See the website of the Shaynoor Dramsi Group

Department of Virology

Pierre Charneau / Yu Wei

Hepatitis B virus infection and liver inflammation in hepatocarcinogenesis

This team main research interests are in host-pathogen interaction during hepatitis B virus (HBV) infection and liver inflammation. HBV infection can cause chronic hepatitis B, which is closely associated with the development of hepatocellular carcinoma (HCC). Inflammation occupies a central position in pathology of liver diseases, including HCC. The team uses cell and mouse models and clinical samples to investigate the role of selective autophagy in HBV infection with a focus on the activities of autophagy receptors. They study the functions of T follicular helper cells (Tfh) and IL-17 in liver inflammation as well as inflammation-associated hepatocarcinogenesis.

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Antoine Gessain

Epidemiology of oncogenic viruses (e.g. HHV-8/KSHV and HTLV)

Study of prevalence, genomic diversity, and modes of transmission of oncogenic viruses, throughout the globe (Central Africa, Australo-Melanesia, South America); Study of mechanims of evolution; This team was the first to evidence recombination in HTLV-1;

Study of zoonotic transmission of oncogenic viruses (different molecular genotypes of HTLV-1).

Transmission of the oncoretrovirus HTLV from mother to child (during breastfeeding)

HTLV-1 is the etiological agent of adult T cell leukemia (ATL) a very severe lymphoproliferation. It occurs in individuals infected during childhood. The team thus study the mechanism of viral dissemination across the intestinal barrier, which can occur during long-term breast-feeding from an HTLV-1 infected mother. Moreover, in collaboration with research groups from Institut Necker, APHP and Institut Curie (PI: Vahid Asnafi, Olivier Hermine and Jacques Ghysdael), they are developing a mouse model of xenografts with ATL cells from patients in order to test leukemic mechanisms and the efficiency of new therapeutic approaches.

Alteration of the microenvironment during HTLV-1 infection

Cancer often develops in a favorable, pro-tumoral microenvironment. The team studies the alterations of the microenvironment that occur upon HTLV infection. They have studied the importance of leukotriene B4 in viral propagation, and are now focusing on the importance of extracellular vesicles (exosomes) in oncogenesis.

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