Lactobacillus rhamnosus GG Orchestrates an Antitumor Immune Response
| Autor: | 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 |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
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 |
| Zdroj: | Cellular and Molecular Gastroenterology and Hepatology, Vol 12, Iss 4, Pp 1311-1327 (2021) Cellular and Molecular Gastroenterology and Hepatology |
| ISSN: | 2352-345X |
| DOI: | 10.1016/j.jcmgh.2021.06.001 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|