Gut microbiota composition is associated with the efficacy of Delta-24-RGDOX in malignant gliomas
Glioblastoma, the most common primary brain tumor, has a 6.8% survival rate 5 years post diagnosis. Our team developed an oncolytic adenovirus with an OX-40L expression cassette named Delta-24-RGDOX. While studies have revealed the interaction between the gut microbiota and immunotherapy agents, no...
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Elsevier
2024-03-01
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| Series: | Molecular Therapy: Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950329924000298 |
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| author | Natalie M. Meléndez-Vázquez Teresa T. Nguyen Xuejun Fan Andrés R. López-Rivas Juan Fueyo Candelaria Gomez-Manzano Filipa Godoy-Vitorino |
| author_facet | Natalie M. Meléndez-Vázquez Teresa T. Nguyen Xuejun Fan Andrés R. López-Rivas Juan Fueyo Candelaria Gomez-Manzano Filipa Godoy-Vitorino |
| author_sort | Natalie M. Meléndez-Vázquez |
| collection | DOAJ |
| description | Glioblastoma, the most common primary brain tumor, has a 6.8% survival rate 5 years post diagnosis. Our team developed an oncolytic adenovirus with an OX-40L expression cassette named Delta-24-RGDOX. While studies have revealed the interaction between the gut microbiota and immunotherapy agents, no studies link the gut microbiota with viroimmunotherapy efficacy in glioblastoma. We hypothesize that gut bacterial signatures will be associated with oncolytic viral therapy efficacy. To test this hypothesis, we evaluated the changes in gut microbiota in two mouse cohorts: (1) GSC-005 glioblastoma-bearing mice treated orally with indoximod, an immunotherapeutic agent, or with Delta-24-RGDOX by intratumoral injection and (2) a mouse cohort harboring GL261-5 tumors used to mechanistically evaluate the importance of CD4+ T cells in relation to viroimmunotherapy efficacy. Microbiota assessment indicated significant differences in the structure of the gut bacterial communities in viroimmunotherapy-treated animals with higher survival compared with control or indoximod-treated animals. Moreover, viroimmunotherapy-treated mice with prolonged survival had a higher abundance of Bifidobacterium. The CD4+ T cell depletion was associated with gut dysbiosis, lower mouse survival, and lower antitumor efficacy of the therapy. These findings suggest that microbiota modulation along the gut-glioma axis contributes to the efficacy and survival of viroimmunotherapy treated animals. |
| format | Article |
| id | doaj-art-05dc18ff379449b4a636ef9d63769adf |
| institution | Kabale University |
| issn | 2950-3299 |
| language | English |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncology |
| spelling | doaj-art-05dc18ff379449b4a636ef9d63769adf2024-11-24T04:15:32ZengElsevierMolecular Therapy: Oncology2950-32992024-03-01321200787Gut microbiota composition is associated with the efficacy of Delta-24-RGDOX in malignant gliomasNatalie M. Meléndez-Vázquez0Teresa T. Nguyen1Xuejun Fan2Andrés R. López-Rivas3Juan Fueyo4Candelaria Gomez-Manzano5Filipa Godoy-Vitorino6Department of Microbiology and Medical Zoology, University of Puerto Rico, School of Medicine, Medical Sciences Campus, San Juan 00918 PR, USADepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Corresponding author Candelaria Gomez-Manzano, Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.Department of Microbiology and Medical Zoology, University of Puerto Rico, School of Medicine, Medical Sciences Campus, San Juan 00918 PR, USA; Corresponding author Filipa Godoy-Vitorino, Department of Microbiology and Medical Zoology, University of Puerto Rico, School of Medicine, Medical Sciences Campus, San Juan, PR 00918, USA.Glioblastoma, the most common primary brain tumor, has a 6.8% survival rate 5 years post diagnosis. Our team developed an oncolytic adenovirus with an OX-40L expression cassette named Delta-24-RGDOX. While studies have revealed the interaction between the gut microbiota and immunotherapy agents, no studies link the gut microbiota with viroimmunotherapy efficacy in glioblastoma. We hypothesize that gut bacterial signatures will be associated with oncolytic viral therapy efficacy. To test this hypothesis, we evaluated the changes in gut microbiota in two mouse cohorts: (1) GSC-005 glioblastoma-bearing mice treated orally with indoximod, an immunotherapeutic agent, or with Delta-24-RGDOX by intratumoral injection and (2) a mouse cohort harboring GL261-5 tumors used to mechanistically evaluate the importance of CD4+ T cells in relation to viroimmunotherapy efficacy. Microbiota assessment indicated significant differences in the structure of the gut bacterial communities in viroimmunotherapy-treated animals with higher survival compared with control or indoximod-treated animals. Moreover, viroimmunotherapy-treated mice with prolonged survival had a higher abundance of Bifidobacterium. The CD4+ T cell depletion was associated with gut dysbiosis, lower mouse survival, and lower antitumor efficacy of the therapy. These findings suggest that microbiota modulation along the gut-glioma axis contributes to the efficacy and survival of viroimmunotherapy treated animals.http://www.sciencedirect.com/science/article/pii/S2950329924000298MT: Regular Issuegut microbiotaviroimmunotherapyglioblastomaoncolytic virusDelta-24-RGDOX |
| spellingShingle | Natalie M. Meléndez-Vázquez Teresa T. Nguyen Xuejun Fan Andrés R. López-Rivas Juan Fueyo Candelaria Gomez-Manzano Filipa Godoy-Vitorino Gut microbiota composition is associated with the efficacy of Delta-24-RGDOX in malignant gliomas Molecular Therapy: Oncology MT: Regular Issue gut microbiota viroimmunotherapy glioblastoma oncolytic virus Delta-24-RGDOX |
| title | Gut microbiota composition is associated with the efficacy of Delta-24-RGDOX in malignant gliomas |
| title_full | Gut microbiota composition is associated with the efficacy of Delta-24-RGDOX in malignant gliomas |
| title_fullStr | Gut microbiota composition is associated with the efficacy of Delta-24-RGDOX in malignant gliomas |
| title_full_unstemmed | Gut microbiota composition is associated with the efficacy of Delta-24-RGDOX in malignant gliomas |
| title_short | Gut microbiota composition is associated with the efficacy of Delta-24-RGDOX in malignant gliomas |
| title_sort | gut microbiota composition is associated with the efficacy of delta 24 rgdox in malignant gliomas |
| topic | MT: Regular Issue gut microbiota viroimmunotherapy glioblastoma oncolytic virus Delta-24-RGDOX |
| url | http://www.sciencedirect.com/science/article/pii/S2950329924000298 |
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