Lactobacillus rhamnosus GG Orchestrates an Antitumor Immune Response
| العنوان: | Lactobacillus rhamnosus GG Orchestrates an Antitumor Immune Response |
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| المؤلفون: | Rheinallt M. Jones, Bejan Saeedi, Richard U. Eboka, Trevor Darby, Joshua A. Owens, Crystal Naudin, Sarah Hunter-Chang, Maria E. Barbian, Lauren Askew, Brian S. Robinson |
| المصدر: | Cellular and Molecular Gastroenterology and Hepatology, Vol 12, Iss 4, Pp 1311-1327 (2021) Cellular and Molecular Gastroenterology and Hepatology |
| بيانات النشر: | Elsevier BV, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, medicine.medical_treatment, Cell Communication, RC799-869, CD8-Positive T-Lymphocytes, LGG, Lactobacillus rhamnosus GG, Mice, DC, dendritic cell, PCR, polymerase chain reaction, 0302 clinical medicine, Neoplasms, Medicine, Intestinal Mucosa, Original Research, Cancer, PD-1, anti programmed cell death protein 1, biology, Lacticaseibacillus rhamnosus, LGG, Gastroenterology, Human microbiome, CFSE, carboxyfluorescein succinimidyl ester, HBSS, Hank’s buffered salt solution, MSI, microsatellite instability, Diseases of the digestive system. Gastroenterology, FCM, flow cytometry, Tumor Burden, CRC, mLn, mesenteric lymph node, CRC, colorectal cancer, MSH, MutS Homolog, 030211 gastroenterology & hepatology, Signal Transduction, TLR, Toll-like receptor, Colon, BMDC, bone-marrow–derived dendritic cell, PBS, phosphate-buffered saline, DSS-AOM, dextran sulfate sodium–azoxymethane, Immunomodulation, 03 medical and health sciences, Immune system, FBS, fetal bovine serum, Lactobacillus rhamnosus, Animals, Humans, Microbiome, CXCL, chemokine ligands, Host Microbial Interactions, Hepatology, CD8 T Cells, business.industry, Probiotics, Immunity, Dendritic Cells, Immunotherapy, Dendritic cell, biology.organism_classification, medicine.disease, WT, wild-type, Toll-Like Receptor 2, Gastrointestinal Microbiome, IL, interleukin, Disease Models, Animal, TLR2, 030104 developmental biology, Immunology, business, BC, Bacillus cereus |
| الوصف: | Background & Aims In colorectal cancer, approximately 95% of patients are refractory to immunotherapy because of low antitumor immune responses. Therefore, there is an exigent need to develop treatments that increase antitumor immune responses and decrease tumor burden to enhance immunotherapy. Methods The gut microbiome has been described as a master modulator of immune responses. We administered the human commensal, Lactobacillus rhamnosus GG (LGG), to mice and characterized the changes in the gut immune landscape. Because the presence of lactobacilli in the gut microbiome has been linked with decreased tumor burden and antitumor immune responses, we also supplemented a genetic and a chemical model of murine intestinal cancer with LGG. For clinical relevance, we therapeutically administered LGG after tumors had formed. We also tested for the requirement of CD8 T cells in LGG-mediated modulation of gut tumor burden. Results We detected increased colonic CD8 T-cell responses specifically in LGG-supplemented mice. The CD8 T-cell induction was dependent on dendritic cell activation mediated via Toll-like receptor-2, thereby describing a novel mechanism in which a member of the human microbiome induces an intestinal CD8 T-cell response. We also show that LGG decreased tumor burden in the murine gut cancer models by a CD8 T-cell–dependent manner. Conclusions These data support the potential use of LGG to augment antitumor immune responses in colorectal cancer patients and ultimately for increasing the breadth and efficacy of immunotherapy. Graphical abstract |
| تدمد: | 2352-345X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f8a2842f4bdfc40a2fd1a616f50f932c https://doi.org/10.1016/j.jcmgh.2021.06.001 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....f8a2842f4bdfc40a2fd1a616f50f932c |
| قاعدة البيانات: | OpenAIRE |
Full Text via ClinicalKey | تدمد: | 2352345X |
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