Abstract IA38: Manipulating the gut microbiome to improve immunotherapy of melanoma
| Autor: | Carmine Menna, Amirin Dzutsev, Marie Vétizou, Jonathan H. Badger, John M. Kirkwood, John McCullogh, Hassane M. Zarour, Giorgio Trinchieri, Diwakar Davar, Ornella Pagliano |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research biology business.industry medicine.medical_treatment Melanoma T cell Immunology Cancer Immunotherapy Gut flora medicine.disease biology.organism_classification Blockade 03 medical and health sciences 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Immune system Cancer immunotherapy 030220 oncology & carcinogenesis medicine Cancer research business |
| Zdroj: | Cancer Immunology Research. 7:IA38-IA38 |
| ISSN: | 2326-6074 2326-6066 |
| Popis: | Immunotherapy with blocking anti-PD1 monoclonal antibodies (a PD1 mAbs) has become one of the most potent therapies of melanoma, providing extended clinical benefits to 30-40% advanced melanoma patients. There is substantial evidence that pre-existing tumor-infiltrating CD8+T cell infiltrates correlate with clinical antitumor response to PD1 blockade. However, not all T cell-inflamed tumors respond to PD1 blockade and not all melanomas are inflamed. Hence, the mechanisms supporting response or resistance to PD1 blockade remain to be precisely determined. One intriguing finding in the field of cancer immunotherapy is the recent demonstration that the gut microbiome regulates immune and clinical responses to PD1 blockade in murine tumor models. Mice with distinct gut microbiota profiles exhibited differential tumor growth, eliminated upon cohousing. This difference was transmittable and augmented the clinical efficacy of PD1 blockade. Interestingly, fecal microbiota transplant (FMT) together with aPD1 mAbs resulted in nearly full tumor rejection in mice with melanoma. Multiple studies have recently correlated the presence of specific bacterial commensal profile with response to PD-1 blockade in melanoma. To investigate the relevance of these findings in melanoma patients, we have collected stool from melanoma patients treated with aPD-1 mAbs. Using metagenomics, we evaluated whether PD-1 responders and PD-1 non-responders exhibited a distinct gut microbiota profile and whether the gut microbiota profile overlaps with previously published studies. We have also implemented a novel clinical trial with fecal microbiota transplant (FMT) FMT obtained from long-term PD1 responders combined with PD1 blockade in melanoma patients who failed to respond to PD1 blockade alone. This trial will determine whether the administration of a single PD1 responder-derived FMT to PD1 non-responders together with PD1 blockade is safe and can promote clinical and immune antitumor response to melanoma. Citation Format: Diwakar Davar, Marie Anne Vetizou, Amirin Dzutsev, Jonathan Badger, John McCullogh, Carmine Menna, Ornella Pagliano, John M. Kirkwood, Giorgio Trinchieri, Hassane M. Zarour. Manipulating the gut microbiome to improve immunotherapy of melanoma [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr IA38. |
| Databáze: | OpenAIRE |
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