Colibactin‐positive Escherichia coli induce a procarcinogenic immune environment leading to immunotherapy resistance in colorectal cancer

Autor: Al Hassan Casse, Guillaume Carrier, Pierre Sauvanet, Souad Naimi, Franck Pagès, Nicolas Barnich, Mathilde Bonnet, Romain Villeger, Elisabeth Billard, Arnaud Briat, Denis Pezet, Amélie Lopès, Gwenaëlle Roche, Julie Veziant, Bruno Dumas
Přispěvatelé: Sanofi [Vitry-sur-Seine], SANOFI Recherche, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Chirurgie Digestive et Hépatobiliaire [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Laboratoire d’immunologie [Hôpital Européen Georges Pompidou - APHP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CIFRE grant [2015/622], Ligue contre le cancer 63/03 [2018], ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016), European Project: AV001826/AV0010859,CPER, École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Cancer Research
Lymphocyte T
Neutrophils
Colorectal cancer
medicine.medical_treatment
Programmed Cell Death 1 Receptor
CD8-Positive T-Lymphocytes
Microenvironnement immunitaire
Cancer colorectal
Mice
0302 clinical medicine
T-cell
Tumor Microenvironment
Mesenteric lymph nodes
biology
Colibactin
Colibactine
3. Good health
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Colonic Neoplasms
Female
Immunotherapy
medicine.symptom
T cell
CD3
Inflammation
[SDV.CAN]Life Sciences [q-bio]/Cancer
03 medical and health sciences
Lymphocytes
Tumor-Infiltrating
Immune system
Escherichia coli
medicine
Animals
Humans
Lymphocyte Count
business.industry
E. coli
medicine.disease
digestive system diseases
Mice
Inbred C57BL
Immune microenvironment
Drug Resistance
Neoplasm
Polyketides
Cancer research
biology.protein
Peptides
business
CD8
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Zdroj: International Journal of Cancer
International Journal of Cancer, 2020, 146 (11), pp.3147-3159. ⟨10.1002/ijc.32920⟩
International Journal of Cancer, Wiley, 2020, 146 (11), pp.3147-3159. ⟨10.1002/ijc.32920⟩
ISSN: 0020-7136
1097-0215
Popis: International audience; Colibactin-producing E. coli (CoPEC) are frequently detected in colorectal cancer (CRC) and exhibit procarcinogenic properties. Because increasing evidence show the role of immune environment and especially of antitumor T-cells in CRC development, we investigated the impact of CoPEC on these cells in human CRC and in the APC(Min/+) mice colon. T-cell density was evaluated by immunohistochemistry in human tumors known for their CoPEC status. APC(min/+) mice were chronically infected with a CoPEC strain (11G5). Immune cells (neutrophils and T-cell populations) were then quantified by immunofluorescent staining of the colon. The quantification of lymphoid populations was also performed in the mesenteric lymph nodes (MLNs). Here, we show that the colonization of CRC patients by CoPEC is associated with a decrease of tumor-infiltrating T lymphocytes (CD3(+) T-cells). Similarly, we demonstrated, in mice, that CoPEC chronic infection decreases CD3(+) and CD8(+) T-cells and increases colonic inflammation. In addition, we noticed a significant decrease in antitumor T-cells in the MLNs of CoPEC-infected mice compared to that of controls. Moreover, we show that CoPEC infection decreases the antimouse PD-1 immunotherapy efficacy in MC38 tumor model. Our findings suggest that CoPEC could promote a procarcinogenic immune environment through impairment of antitumor T-cell response, leading to tumoral resistance to immunotherapy. CoPEC could thus be a new biomarker predicting the anti-PD-1 response in CRC.
Databáze: OpenAIRE
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