المؤلفون: Tapia-Galisteo, Antonio, Sánchez-Rodríguez, Iñigo, Narbona, Javier, Iglesias-Hernández, Patricia, Aragón-García, Saray, Jiménez-Reinoso, Anaïs, Compte, Marta, Khan, Shaukat, Tsuda, Takeshi, Chames, Patrick, Lacadena, Javier, Álvarez-Vallina, Luis, Sanz, Laura

المساهمون: Hospital Universitario Puerta de Hierro-Majadahonda Madrid, Spain, Instituto de Salud Carlos III Madrid (ISC), Universidad Complutense de Madrid = Complutense University of Madrid Madrid (UCM), Hospital Universitario 12 de Octubre Madrid, Leadartis Sl, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes (IPC), Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes (IPC), Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)

المصدر: ISSN: 2162-4011.

مصطلحات موضوعية: Bispecific antibody, trispecific antibody, T-cell engager, CAR-T cell, cancer immunotherapy, combination therapy, colorectal cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology

الوصف: International audience ; T cell-based immunotherapies for solid tumors have not achieved the clinical success observed in hematological malignancies, partially due to the immunosuppressive effect promoted by the tumor microenvironment, where PD-L1 and TGF-β play a pivotal role. However, durable responses to immune checkpoint inhibitors remain limited to a minority of patients, while TGF-β inhibitors have not reached the market yet. Here, we describe a bispecific antibody for dual blockade of PD-L1 and TFG-β, termed AxF (scFv)$_2$, under the premise that combination with T cell redirecting strategies would improve clinical benefit. The AxF (scFv)$_2$ antibody was well expressed in mammalian and yeast cells, bound both targets and inhibited dose-dependently the corresponding signaling pathways in luminescence-based cellular reporter systems. Moreover, combined treatment with trispecific T-cell engagers (TriTE) or CAR-T cells significantly boosted T cell activation status and cytotoxic response in breast, lung and colorectal (CRC) cancer models. Importantly, the combination of an EpCAMxCD3×EGFR TriTE with the AxF (scFv)$_2$ delayed CRC tumor growth in vivo and significantly enhanced survival compared to monotherapy with the trispecific antibody. In summary, we demonstrated the feasibility of concomitant blockade of PD-L1 and TGF-β by a single molecule, as well as its therapeutic potential in combination with different T cell redirecting agents to overcome tumor microenvironment-mediated immunosuppression.

العلاقة: hal-04583762; https://hal.science/hal-04583762Test; https://hal.science/hal-04583762/documentTest; https://hal.science/hal-04583762/file/Combination%20of%20T%20cell-redirecting%20strategies%20with%20a%20bispecific%20antibody%20blocking%20TGF-%20%20and%20PD-L1%20enhances%20antitumor%20responses.pdfTest

الإتاحة: https://doi.org/10.1080/2162402X.2024.2338558Test
https://hal.science/hal-04583762Test
https://hal.science/hal-04583762/documentTest
https://hal.science/hal-04583762/file/Combination%20of%20T%20cell-redirecting%20strategies%20with%20a%20bispecific%20antibody%20blocking%20TGF-%20%20and%20PD-L1%20enhances%20antitumor%20responses.pdfTest

المؤلفون: Wargny, Matthieu, Goronflot, Thomas, Rimbert, Antoine, Boursier, Jérôme, Kab, Sofiane, Henny, Joseph, Lainé, Antoine, Leux, Christophe, Smati, Sarra, Hadjadj, Samy, Le May, Cédric, Goldberg, Marcel, Zins, Marie, Cariou, Bertrand

المساهمون: Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes), ITX-lab unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Université Paris-Saclay

المصدر: ISSN: 0168-8278.

مصطلحات موضوعية: Hypobetalipoproteinemia, administrative health records, cirrhosis, liver cancer, low density lipoprotein, population-based cohorts, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie

الوصف: International audience ; Background & aims: Beyond cardiovascular disease protection, the health consequences of very low low-density lipoprotein-cholesterol (LDL-C) concentration remain a matter of debate. In primary hypobetalipoproteinemia (HBL), liver steatosis and cirrhosis have been occasionally reported. Here, we aimed to investigate the association between HBL and the risk of hepatic complications (cirrhosis complication and/or primary liver cancer) in the general population.Methods: A cohort study was conducted in the French population-based cohort CONSTANCES. Participants with primary HBL (LDL-C<5th percentile for age and sex, [HBL]) were compared with those with normal LDL-C concentrations (40th-60th percentile, [Control]). Participants on lipid-lowering therapies were excluded. For hepatic complications, follow-up events were compared by calculating the incidence density ratio (IDR). The same analyses were replicated in the UK Biobank (UKBB) cohort.Results: In the CONSTANCES and UKBB cohorts, 34,653 and 94,666 patients were analyzed, with median age of 45 and 56 years, mean LDL-C concentrations (HBL vs. Control) 71 vs. 128 mg/dL and 86 vs. 142 mg/dL, and mean follow-up of 5.0 and 11.5 years, respectively. The HBL group presented a higher incidence of hepatic complications than the control group: 0.32/1000 vs. 0.07/1000 person-years (IDR=4.50, 95%CI 1.91-10.6) in CONSTANCES, and 0.69/1000 vs. 0.21/1000 person-years (IDR=3.27, 95%CI 2.63-4.06) in UKBB. This risk proved to be independent of classic liver-disease risk factors (obesity, alcohol consumption, diabetes, viral hepatitis), including in a 5-year landmark analysis excluding early events. Sensitivity analyses replacing LDL-C by apoliprotein-B, or by individuals with genetically defined HBL, showed similar results.Conclusions: HBL is associated with a markedly increased risk of hepatic complications. HBL must be considered as a substantial independent risk factor for liver diseases which justifies specific prevention and screening.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/38331324; hal-04474613; https://hal.science/hal-04474613Test; https://hal.science/hal-04474613/documentTest; https://hal.science/hal-04474613/file/PIIS0168827824001089.pdfTest; PUBMED: 38331324

الإتاحة: https://doi.org/10.1016/j.jhep.2024.01.030Test
https://hal.science/hal-04474613Test
https://hal.science/hal-04474613/documentTest
https://hal.science/hal-04474613/file/PIIS0168827824001089.pdfTest

المؤلفون: Ruiz, Eloy, Honles, Jorge, Fernández, Ramiro, Uribe, Karla, Cerapio, Juan Pablo, Cancino, Karina, Contreras-Mancilla, Juan, Casavilca-Zambrano, Sandro, Berrospi, Francisco, Pineau, Pascal, Bertani, Stéphane

المساهمون: Instituto Nacional de Enfermedades Neoplasicas Lima, Pérou (INEN), Laboratoire Mixte International d'Oncologie Anthropologique Moléculaire = International Joint Laboratory of Molecular Anthropological Oncology (LOAM), Institut de Recherche pour le Développement (IRD Pérou ), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universidad Peruana Cayetano Heredia (UPCH), Universidad de Huánuco Huánuco, Pérou, Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur Paris (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), This work was supported by ITMO Cancer of the French National Alliance for Life Sciences and Health (Aviesan) and the French National Cancer Institute (INCa) on funds administered by the French National Institute of Health andMedical Research (Inserm), grant agreement 21CD025-00. K.C. was the recipient of a doctoral fellowship from the Research Grants for a Thesis in the South (ARTS) program of the French National Research Institute for Sustainable Development (IRD), fellowship agreement IRD-ARTS-AO2022, J.C.M. was the recipient of a doctoral fellowship from the Peruvian National Science and Technology Council (Concytec) and the World Bank on funds administered by the Peruvian National Scientific Research and Advanced Studies Program (ProCiencia), fellowship agreement 08-2018-FONDECYT/BM.

المصدر: ISSN: 1365-182X.

مصطلحات موضوعية: [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology

الوصف: International audience ; Background: Liver resection is the mainstay treatment option for patients with hepatocellular carcinoma in the non-cirrhotic liver (NCL-HCC), but almost half of these patients will experience a recurrence within five years of surgery. Therefore, we aimed to develop a rationale-based risk evaluation tool to assist surgeons in recurrence-related treatment planning for NCL-HCC. Methods: We analyzed single-center data from 263 patients who underwent liver resection for NCL-HCC. Using machine learning modeling, we first determined an optimal cut-off point to discriminate early versus late relapses based on time to recurrence. We then constructed a risk score based on preoperative variables to forecast outcomes according to recurrence-free survival. Results: We computed an optimal cut-off point for early recurrence at 12 months post-surgery. We identified macroscopic vascular invasion, multifocal tumor, and spontaneous tumor rupture as predictor variables of outcomes associated with early recurrence and integrated them into a scoring system. We thus stratified, with high concordance, three groups of patients on a graduated scale of recurrence-related survival. Conclusion: We constructed a preoperative risk score to estimate outcomes after liver resection in NCL-HCC patients. Hence, this score makes it possible to rationally stratify patients based on recurrence risk assessment for better treatment planning.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/38431511; hal-04460446; https://hal.science/hal-04460446Test; https://hal.science/hal-04460446/documentTest; https://hal.science/hal-04460446/file/PIIS1365182X24000297.pdfTest; PUBMED: 38431511

الإتاحة: https://doi.org/10.1016/j.hpb.2024.02.010Test
https://hal.science/hal-04460446Test
https://hal.science/hal-04460446/documentTest
https://hal.science/hal-04460446/file/PIIS1365182X24000297.pdfTest

المؤلفون: Nguyen Van, Rémi, Houssel‐debry, Pauline, Erard, Domitille, Dumortier, Jérôme, Pouvaret, Anne, Bergez, Guillaume, Danion, François, Surgers, Laure, Le-Moing, Vincent, Kamar, Nassim, Lanternier, Fanny, Tattevin, Pierre

المساهمون: Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Ponchaillou, Hôpital de la Croix-Rousse CHU - HCL, Hospices Civils de Lyon (HCL), Hôpital Edouard Herriot CHU - HCL, Centre Hospitalier Universitaire de Saint-Etienne CHU Saint-Etienne (CHU ST-E), Hôpital Beaujon AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immuno-Rhumatologie Moléculaire (IRM), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Montpellier, Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Necker - Enfants Malades AP-HP, ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), None

المصدر: ISSN: 2666-9919 ; Infectious Diseases Now ; https://hal.science/hal-04483646Test ; Infectious Diseases Now, 2024, Infectious Diseases Now, 54 (3), pp.104869. ⟨10.1016/j.idnow.2024.104869⟩.

مصطلحات موضوعية: latent tuberculosis, liver transplant, pre-transplant screening, prevention, tuberculosis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology

الوصف: International audience ; Background - Liver transplant recipients are at risk of tuberculosis, which is particularly difficult-to diagnose and to treat in this population. Methods - Retrospective study of all cases of tuberculosis diagnosed from 2007 to 2022 in the French network of liver transplant sites. Results - Twenty-three liver transplant recipients were diagnosed with tuberculosis (six females, median age 59 years [interquartile range, 54-62]), with a median time lapse of 10 months [5-40.5] after transplant, and 38 days [26-60] after symptoms onset. Primary modes of pathogenesis were latent tuberculosis reactivation (n = 15) and transplant-related transmission (n = 3). Even though most patients with pre-transplant data had risk factors for tuberculosis (11/20), IFN-gamma release assay was performed in only three. Most cases involved extra-pulmonary tuberculosis (20/23, 87 %). With median follow-up of 63 months [24-108], five patients died (22 %), including four tuberculosis-related deaths. Conclusions - Extrapulmonary tuberculosis is a severe disease in liver transplant recipients. Systematic pre-transplant screening of latent tuberculosis may prevent most of them.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/38401760; hal-04483646; https://hal.science/hal-04483646Test; https://hal.science/hal-04483646/documentTest; https://hal.science/hal-04483646/file/Nguyen%20Van%20et%20al.%20-%202024%20-%20Characteristics,%20management,%20and%20outcome%20of%20tuberc.pdfTest; PUBMED: 38401760

الإتاحة: https://doi.org/10.1016/j.idnow.2024.104869Test
https://hal.science/hal-04483646Test
https://hal.science/hal-04483646/documentTest
https://hal.science/hal-04483646/file/Nguyen%20Van%20et%20al.%20-%202024%20-%20Characteristics,%20management,%20and%20outcome%20of%20tuberc.pdfTest

المؤلفون: Lachiondo-Ortega, Sofia, Rejano-Gordillo, Claudia, M, Simon, Jorge, Lopitz-Otsoa, Fernando, C. Delgado, Teresa, Mazan-Mamczarz, Krystyna, Goikoetxea-Usandizaga, Naroa, Zapata-Pavas, L. Estefanía, García-del Río, Ana, Guerra, Pietro, Peña-Sanfélix, Patricia, Hermán-Sánchez, Natalia, Al-Abdulla, Ruba, Fernandez-Rodríguez, Carmen, Azkargorta, Mikel, Velázquez-Cruz, Alejandro, Guyon, Joris, Martín, César, Zalamea, Juan, Diego, Egia-Mendikute, Leire, Sanz-Parra, Arantza, Serrano-Maciá, Marina, González-Recio, Irene, Gonzalez-Lopez, Monika, Martínez-Cruz, Luis, Alfonso, Pontisso, Patrizia, Aransay, Ana, M, Barrio, Rosa, Sutherland, James, D, Abrescia, Nicola, G A, Elortza, Félix, Lujambio, Amaia, Banales, Jesus, M, Luque, Raúl, M, Gahete, Manuel, D, Palazón, Asís, Avila, Matias, A, G. Marin, Jose, J, De, Supriyo, Daubon, Thomas, Díaz-Quintana, Antonio, Díaz-Moreno, Irene, Gorospe, Myriam, Rodriguez, Manuel S, Martínez-Chantar, María, Luz

المساهمون: Center for Cooperative Research in Biosciences = Centro de Investigación cooperativa en biociencia (Derio, Biscay, Espagne) (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Universidad de Extremadura - University of Extremadura (UEX), Biofisika Institute (CSIC, UPV/EHU), 48940 Leioa, Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, Università degli Studi di Padova = University of Padua (Unipd), Instituto Maimonides de Investigación Biomédica de Cordoba (IMIBIC), Universidad de Córdoba = University of Córdoba Córdoba -Hospital Universitario Reina Sofía, Universidad Miguel Hernández Elche (UMH), University of Medicine Greifswald, Universidad Pública de Navarra Espagne = Public University of Navarra (UPNA), Scientific Research Centre 'Isla de la Cartuja' (cicCartuja), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Bordeaux (CHU de Bordeaux), Universidad del Pais Vasco / Euskal Herriko Unibertsitatea Espagne (UPV/EHU), Ikerbasque - Basque Foundation for Science, Icahn School of Medicine at Mount Sinai New York (MSSM), BIODonostia Research Institute, Center for Applied Medical Research Plamplona (CIMA), Universidad de Navarra Pamplona (UNAV), Navarra Institute for Health Research / Instituto de Investigación Sanitaria de Navarra (IdiSNA), Universidad Pública de Navarra Espagne = Public University of Navarra (UPNA)-Universidad de Navarra Pamplona (UNAV)-Clínica Universidad de Navarra Pamplona, Instituto de Investigación Biomédica de Salamanca (IBSAL), Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)

المصدر: ISSN: 2211-1247.

مصطلحات موضوعية: ELAVL1, SUMO, PTMs, Senescence, HCC, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology

الوصف: International audience ; The posttranslational modification of proteins critically influences many biological processes and is a key mechanism that regulates the function of the RNA-binding protein Hu antigen R (HuR), a hub in liver cancer. Here, we show that HuR is SUMOylated in the tumor sections of patients with hepatocellular carcinoma in contrast to the surrounding tissue, as well as in human cell line and mouse models of the disease. SUMOylation of HuR promotes major cancer hallmarks, namely proliferation and invasion, whereas the absence of HuR SUMOylation results in a senescent phenotype with dysfunctional mitochondria and endoplasmic reticulum. Mechanistically, SUMOylation induces a structural rearrangement of the RNA recognition motifs that modulates HuR binding affinity to its target RNAs, further modifying the transcriptomic profile toward hepatic tumor progression. Overall, SUMOylation constitutes a mechanism of HuR regulation that could be potentially exploited as a therapeutic strategy for liver cancer.

العلاقة: hal-04522023; https://hal.science/hal-04522023Test; https://hal.science/hal-04522023/documentTest; https://hal.science/hal-04522023/file/Lachiondo-Ortega,%20SUMOylation%20controls%20Hu%20antigen%20R,%202024.pdfTest

الإتاحة: https://doi.org/10.1016/j.celrep.2024.113924Test
https://hal.science/hal-04522023Test
https://hal.science/hal-04522023/documentTest
https://hal.science/hal-04522023/file/Lachiondo-Ortega,%20SUMOylation%20controls%20Hu%20antigen%20R,%202024.pdfTest

المؤلفون: Gouez, Manon, Rébillard, Amélie, Thomas, Amandine, Beaumel, Sabine, Matera, Eva-Laure, Gouraud, Etienne, Orfila, Luz, Martin, Brice, Pérol, Olivia, Chaveroux, Cedric, Chirico, Erica N., Dumontet, Charles, Fervers, Béatrice, Pialoux, Vincent

المساهمون: Centre Léon Bérard Lyon, Laboratoire Mouvement Sport Santé (M2S), Université de Rennes (UR)-École normale supérieure - Rennes (ENS Rennes)-Université de Brest (UBO)-Université de Rennes 2 (UR2)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Université Savoie Mont Blanc (USMB Université de Savoie Université de Chambéry ), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard Lyon -Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité Ad Hoc INSERM 000008 "Radiations : Défense, Santé, Environnement" Lyon (Inserm U1296), Centre Léon Bérard Lyon -Université Lumière - Lyon 2 (UL2)-Service de Santé des Armées-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Cooper Medical School of Rowan University Camden (CMSRU), This work was supported by the Ligue Contre Le Cancer Auvergne Rhone Alpes. MG was supported by the French Ministry of Education, Research and Innovation.

المصدر: ISSN: 1664-3224.

مصطلحات موضوعية: colorectal cancer, acute exercise, immune check point inhibitor, immune cell, cancer immunotherapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology

الوصف: International audience ; Acute exercise induces transient modifications in the tumor microenvironment and has been linked to reduced tumor growth along with increased infiltration of immune cells within the tumor in mouse models. In this study, we aimed to evaluate the impact of acute exercise before treatment administration on tumor growth in a mice model of MC38 colorectal cancer receiving an immune checkpoint inhibitor (ICI) and chemotherapy. Six-week-old mice injected with colorectal cancer cells (MC38) were randomized in 4 groups: control (CTRL), immuno-chemotherapy (TRT), exercise (EXE) and combined intervention (TRT/EXE). Both TRT and TRT-EXE received ICI: anti-PD1-1 (1 injection/week) and capecitabine + oxaliplatin (5 times a week) for 1 week (experimentation 1), 3 weeks (experimentation 2). TRT-EXE and EXE groups were submitted to 50 minutes of treadmill exercise before each treatment administration. Over the protocol duration, tumor size has been monitored daily. Tumor growth and microenvironment parameters were measured after the intervention on Day 7 (D7) and Day 16 (D16). From day 4 to day 7, tumor volumes decreased in the EXE/TRT group while remaining stable in the TRT group (p=0.0213). From day 7 until day 16 tumor volume decreased with no significant difference between TRT and TRT/EXE. At D7 the TRT/EXE group exhibited a higher total infiltrate T cell (p=0.0118) and CD8+ cytotoxic T cell (p=0.0031). At D16, tumor marker of apoptosis, vascular integrity and inflammation were not significantly different between TRT and TRT/EXE. Our main result was that acute exercise before immuno-chemotherapy administration significantly decreased early-phase tumor growth (D0 to D4). Additionally, exercise led to immune cell infiltration changes during the first week after exercise, while no significant molecular alterations in the tumor were observed 3 weeks after exercise.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/38426110; hal-04479752; https://hal.science/hal-04479752Test; https://hal.science/hal-04479752/documentTest; https://hal.science/hal-04479752/file/fimmu-15-1368550.pdfTest; PUBMED: 38426110

الإتاحة: https://doi.org/10.3389/fimmu.2024.1368550Test
https://hal.science/hal-04479752Test
https://hal.science/hal-04479752/documentTest
https://hal.science/hal-04479752/file/fimmu-15-1368550.pdfTest

المؤلفون: Quénéhervé, Lucille, Trang-Poisson, Caroline, Fantou, Aurelie, Flamant, Mathurin, Durand, Tony, Bouguen, Guillaume, Brégeon, Jeremy, Oullier, Thibauld, Amil, Morgane, Dewitte, Marie, Bardot, Stephanie, Blandin, Stéphanie, Braudeau, Cecile, Vibet, Marie-Anne, Josien, Regis, Neunlist, Michel, Bourreille, Arnaud

المساهمون: Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), The Enteric Nervous System in gut and brain disorders U1235 (TENS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre d'investigation clinique (CIC) de Nantes -CIC Plurithématique (CIC 0004 - Nantes), Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Centre d'Investigation Clinique Rennes (CIC), Université de Rennes (UR)-Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Ponchaillou -Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Ponchaillou, Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Biological control of artificial ecosystems (BIOCORE), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire d'océanographie de Villefranche (LOV), Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de la Mer de Villefranche (IMEV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de la Mer de Villefranche (IMEV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Financial Disclosure The DETECT study has been funded by the French “Programme hospitalier de Recherche Clinique interregional (PHRC-I)” (AB). The vedolizumab used in this study was provided courtesy of Takeda Pharmaceutical® (Japan). The Dual-band Cellvizio was provided courtesy of by MaunaKea technologies (France). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

المصدر: ISSN: 1932-6203.

مصطلحات موضوعية: [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology

الوصف: International audience ; AIMS: In patients with ulcerative colitis (UC), no biomarker is available to help the physician to choose the most suitable biotherapy. The primary objective of this pilot study was to assess the feasibility of identification of α4β7- and TNF-expressing cells, to predict the response to vedolizumab using confocal laser endoscopy (CLE). METHODS: Patients with moderate-to-severe UC, naïve of biotherapy, received vedolizumab. Clinical evaluation was performed at each infusion. Endoscopic evaluation was performed before inclusion and at week 22. Fresh colonic biopsies were stained using FITC-labelled vedolizumab and Alexa fluor-labelled adalimumab and ex vivo dual-band CLE images were acquired. Blood samples were collected to measure trough concentrations of vedolizumab and to determine absolute counts of T and B cells subpopulations, NK cells and monocytes. RESULTS: Nineteen patients were enrolled in the study and received at least one dose of vedolizumab. Clinical remission and endoscopic improvement were observed in 58% of whom 5 patients (45%) had an endoscopic subscore of 0. In terms of clinical response and remission, endoscopic improvement and histologic response, FITC-conjugated vedolizumab staining tended to be higher in responder patients compared to non-responders at week 22. A threshold value of 6 positive FITC-vedolizumab staining areas detected by CLE seemed informative to discriminate the responders and non-responders. The results were similar in terms of clinical remission and endoscopic improvement with a sensitivity of 78% and a specificity of 85% (p = 0.05). Trough concentrations and blood immune cells were not associated with responses to vedolizumab. CONCLUSION: This pilot study demonstrate that dual-band CLE is feasible to detect α4β7- and TNF-expressing cells. Positive α4β7 staining seems to be associated with clinical and endoscopic remission in UC patients treated by anti-α4β7-integrin, subject to validation by larger-scale studies. Clinical-trial.gov: NCT02878083.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/38564601; hal-04534064; https://hal.science/hal-04534064Test; https://hal.science/hal-04534064/documentTest; https://hal.science/hal-04534064/file/journal.pone.0298313.pdfTest; PUBMED: 38564601

الإتاحة: https://doi.org/10.1371/journal.pone.0298313Test
https://hal.science/hal-04534064Test
https://hal.science/hal-04534064/documentTest
https://hal.science/hal-04534064/file/journal.pone.0298313.pdfTest

المؤلفون: Beaufrère, Aurélie, Ouzir, Nora, Zafar, Paul, Emile, Laurent-Bellue, Astrid, Albuquerque, Miguel, Lubuela, Gwladys, Grégory, Jules, Guettier, Catherine, Mondet, Kévin, Pesquet, Jean-Christophe, Paradis, Valérie

المساهمون: Hôpital Beaujon AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre de vision numérique (CVN), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay, OPtimisation Imagerie et Santé (OPIS), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de vision numérique (CVN), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-CentraleSupélec-Université Paris-Saclay, Service d'anatomie pathologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Hôpital Bicêtre AP-HP, Le Kremlin-Bicêtre, Université Paris Cité (UPCité), McGill University = Université McGill Montréal, Canada, Methods of therapeutic evaluation of chronic diseases, Centre for Research in Epidemiology and Statistics, Conservatoire National des Arts et Métiers CNAM (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers CNAM (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), CLASSTHEP

المصدر: EISSN: 2589-5559 ; JHEP Reports Innovation in Hepatology ; https://hal.science/hal-04534805Test ; JHEP Reports Innovation in Hepatology, 2024, 6 (3), pp.101008. ⟨10.1016/j.jhepr.2024.101008⟩

مصطلحات موضوعية: Primary liver cancer, biopsy, histological slides, artificial intelligence, weakly supervised learning, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI], [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, [INFO.INFO-LG]Computer Science [cs]/Machine Learning [cs.LG], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]

الوصف: International audience ; Background & Aims: The diagnosis of primary liver cancers (PLCs) can be challenging, especially on biopsies and for combined hepatocellular-cholangiocarcinoma (cHCC-CCA). We automatically classified PLCs on routine-stained biopsies using a weakly supervised learning method.Method: We selected 166 PLC biopsies divided into training, internal and external validation sets: 90, 29 and 47 samples, respectively. Two liver pathologists reviewed each whole-slide hematein eosin saffron (HES)-stained image (WSI). After annotating the tumour/non-tumour areas, tiles of 256x256 pixels were extracted from the WSIs and used to train a ResNet18 neural network. The tumour/non-tumour annotations served as labels during training, and the network's last convolutional layer was used to extract new tumour tile features. Without knowledge of the precise labels of the malignancies, we then applied an unsupervised clustering algorithm.Results: Pathological review classified the training and validation sets into hepatocellular carcinoma (HCC, 33/90, 11/29 and 26/47), intrahepatic cholangiocarcinoma (iCCA, 28/90, 9/29 and 15/47), and cHCC-CCA (29/90, 9/29 and 6/47). In the two-cluster model, Clusters 0 and 1 contained mainly HCC and iCCA histological features. The diagnostic agreement between the pathological diagnosis and the two-cluster model predictions (major contingent) in the internal and external validation sets was 100% (11/11) and 96% (25/26) for HCC and 78% (7/9) and 87% (13/15) for iCCA, respectively. For cHCC-CCA, we observed a highly variable proportion of tiles from each cluster (cluster 0: 5-97%; cluster 1: 2-94%).Conclusion: Our method applied to PLC HES biopsy could identify specific morphological features of HCC and iCCA. Although no specific features of cHCC-CCA were recognized, assessing the proportion of HCC and iCCA tiles within a slide could facilitate the identification of cHCC-CCA.Impact and implications: The diagnosis of primary liver cancers can be challenging, especially on biopsies ...

العلاقة: hal-04534805; https://hal.science/hal-04534805Test; https://hal.science/hal-04534805/documentTest; https://hal.science/hal-04534805/file/published_paper.pdfTest

الإتاحة: https://doi.org/10.1016/j.jhepr.2024.101008Test
https://hal.science/hal-04534805Test
https://hal.science/hal-04534805/documentTest
https://hal.science/hal-04534805/file/published_paper.pdfTest

المؤلفون: Bidaud-Meynard, Aurélien, Bourdais, Anne, Nicolle, Ophélie, Duclos, Maela, Saleh, Jad, Ruemmele, Frank, Farin, Henner F., Delacour, Delphine, Moshous, Despina, Michaux, Grégoire

المساهمون: Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Jacques Monod (IJM (UMR_7592)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Biodiversité et Biotechnologie Fongiques (BBF), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), German Cancer Research Center - Deutsches Krebsforschungszentrum Heidelberg (DKFZ), Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS)

المصدر: ISSN: 2352-345X ; Cellular and Molecular Gastroenterology and Hepatology ; https://hal.science/hal-04534129Test ; Cellular and Molecular Gastroenterology and Hepatology, 2024, 17 (6), pp.1072-1075. ⟨10.1016/j.jcmgh.2024.02.011⟩.

مصطلحات موضوعية: [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology

الوصف: International audience

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/38369130; hal-04534129; https://hal.science/hal-04534129Test; https://hal.science/hal-04534129/documentTest; https://hal.science/hal-04534129/file/1-s2.0-S2352345X24000390-main.pdfTest; PUBMED: 38369130

الإتاحة: https://doi.org/10.1016/j.jcmgh.2024.02.011Test
https://hal.science/hal-04534129Test
https://hal.science/hal-04534129/documentTest
https://hal.science/hal-04534129/file/1-s2.0-S2352345X24000390-main.pdfTest

المؤلفون: de Oliveira Alves, Nilmara, Dalmasso, Guillaume, Nikitina, Darja, Vaysse, Amaury, Ruez, Richard, Ledoux, Lea, Pedron, Thierry, Bergsten, Emma, Boulard, Olivier, Autier, Lora, Allam, Sofian, Motreff, Laurence, Sauvanet, Pierre, Letourneur, Diane, Kashyap, Pragya, Gagnière, Johan, Pezet, Denis, Godfraind, Catherine, Salzet, Michel, Lemichez, Emmanuel, Bonnet, Mathilde, Najjar, Imène, Malabat, Christophe, Monot, Marc, Mestivier, Denis, Barnich, Nicolas, Yadav, Pankaj, Fournier, Isabelle, Kennedy, Sean, Mettouchi, Amel, Bonnet, Richard, Sobhani, Iradj, Chamaillard, Mathias

المساهمون: Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret Lille (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille), Laboratoire de Physiologie Cellulaire - U 1003 (PHYCELL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Centre National de la Recherche Scientifique (CNRS), Institut Pasteur Paris (IP), Lithuanian University of health Sciences (LSMU), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur Paris (IP)-Université Paris Cité (UPCité), Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM) - U 1192 (PRISM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille), Pathogénie microbienne moléculaire, Institut Pasteur Paris (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bactériophage, bactérie, hôte - Bacteriophage, bacterium, host, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS), Toxines bactériennes - Bacterial Toxins, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Pôle Biomics (C2RT), Centre de Ressources et de Recherche Technologique - Center for Technological Resources and Research (C2RT), Institut Pasteur Paris (IP)-Institut Pasteur Paris (IP), Indian Institute of Technology Jodhpur (IIT Jodhpur), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Henri Mondor Créteil, Funding support for this research was provided by the follow-ing grants: BpiFrance (grant number R21014EE / RVF21001EEA), Fondation i-SITE (grant number R20086EE / RAK20024EEA), Fondation pour la Recherche Médicale (grant number EQU202103012718), Inserm - Grand Programme Transversal Microbiote (grant number R17075EK/RSE17075EKA and R21091EK/RSE21091EKA), ITMO Cancer AVIESANPlan Cancer (grant number HTE201601,C16067ES/ASC16067ESA) and Région Hauts-de -France START-AIRR program (grant number Start’AIRR- 20-003). We thank the ONCOLille Institute. This work is supported by a grant from Contrat de Plan Etat-Région CPER Cancer 2015-2020.

المصدر: ISSN: 1949-0976.

مصطلحات موضوعية: Colibactin-producing Escherichia coli, land’s cycle, lipid droplet, right-sided colorectal cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology

الوصف: International audience ; Intratumoral bacteria flexibly contribute to cellular and molecular tumor heterogeneity for supporting cancer recurrence through poorly understood mechanisms. Using spatial metabolomic profiling technologies and 16SrRNA sequencing, we herein report that right-sided colorectal tumors are predominantly populated with Colibactin-producing Escherichia coli (CoPEC) that are locally establishing a high-glycerophospholipid microenvironment with lowered immunogenicity. It coincided with a reduced infiltration of CD8+ T lymphocytes that produce the cytotoxic cytokines IFN-γ where invading bacteria have been geolocated. Mechanistically, the accumulation of lipid droplets in infected cancer cells relied on the production of colibactin as a measure to limit genotoxic stress to some extent. Such heightened phosphatidylcholine remodeling by the enzyme of the Land’s cycle supplied CoPEC-infected cancer cells with sufficient energy for sustaining cell survival in response to chemotherapies. This accords with the lowered overall survival of colorectal patients at stage III-IV who were colonized by CoPEC when compared to patients at stage I-II. Accordingly, the sensitivity of CoPEC-infected cancer cells to chemotherapies was restored upon treatment with an acyl-CoA synthetase inhibitor. By contrast, such metabolic dysregulation leading to chemoresistance was not observed in human colon cancer cells that were infected with the mutant strain that did not produce colibactin (11G5∆ClbQ). This work revealed that CoPEC locally supports an energy trade-off lipid overload within tumors for lowering tumor immunogenicity. This may pave the way for improving chemoresistance and subsequently outcome of CRC patients who are colonized by CoPEC.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/38417029; hal-04542255; https://hal.science/hal-04542255Test; https://hal.science/hal-04542255/documentTest; https://hal.science/hal-04542255/file/The%20colibactin-producing%20Escherichia%20coli%20alters%20the%20tumor%20microenvironment%20to%20immunosuppressive%20lipid%20overload%20facilitating%20colorectal%20cancer%20progres.pdfTest; PUBMED: 38417029; PUBMEDCENTRAL: PMC10903627

الإتاحة: https://doi.org/10.1080/19490976.2024.2320291Test
https://hal.science/hal-04542255Test
https://hal.science/hal-04542255/documentTest
https://hal.science/hal-04542255/file/The%20colibactin-producing%20Escherichia%20coli%20alters%20the%20tumor%20microenvironment%20to%20immunosuppressive%20lipid%20overload%20facilitating%20colorectal%20cancer%20progres.pdfTest