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Teng, Nancy M. Y., Malfettone, Andrea, Dalby, Matthew J., Kiu, Raymond, Seki, David, Robinson, Tim, Gion, María, Bermejo, Begonã, Pérez-García, José Manuel, Prat, Aleix, Vázquez, Raúl Márquez, Llombart-Cussac, Antonio, Curigliano, Giuseppe, Schmid, Peter, Barroso-Sousa, Romualdo, Mancino, Mario, Shimizu, Eileen, Rodríguez-Morató, Jose, Mina, Leonardo, Hall, Lindsay J. 
ORCID: https://orcid.org/0000-0001-8938-5709, Robinson, Stephen D. ORCID: https://orcid.org/0000-0002-6606-7588 and Cortés, Javier
(2024)
Profiling the gut and oral microbiota of hormone receptor-positive, HER2-negative metastatic breast cancer patients receiving pembrolizumab and eribulin.
Microbiome Research Reports, 4 (4).
ISSN 2771-5965
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Abstract
Aim: Changes in host-associated microbial communities (i.e., the microbiota) may modulate responses to checkpoint blockade immunotherapy. In the KELLY phase II study (NCT03222856), we previously demonstrated that pembrolizumab [anti-programmed cell death protein 1 (PD-1)] combined with eribulin (plus microtubule-targeting chemotherapy) showed encouraging antitumor activity in patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC) who had received prior treatments. Methods: A total of 58 fecal and 67 saliva samples were prospectively collected from a subset of 28 patients at baseline (BL), after three treatment cycles, and end of treatment. Shotgun metagenomics, 16S rRNA gene amplicon sequencing, and bioinformatics and statistical approaches were used to characterize fecal and oral microbiota profiles. Results: Treatment caused no substantial perturbations in gut or oral microbiota, suggesting minimal drug-related microbial toxicity. Bacteroides and Faecalibacterium were the dominant gut microbiota genera, while Prevotella and Streptococcus were present in both oral and gut samples, highlighting potential gut-oral microbial interactions. Additionally, clinical benefit (CB) appeared to be associated with gut-associated Bacteroides fragilis (B. fragilis) and a BL oral abundance of Streptococcus ≥ 30%. Notably, B. fragilis NCTC 9343 supernatant induced dose-dependent lactate dehydrogenase (LDH) release from the MCF-7 (HR-positive/HER2-negative) BC cell line. Conclusion: These findings suggest that specific gut and oral microbiota may modulate the effectiveness of combinatory anti-BC therapies, potentially through the action of microbial metabolites.
| Item Type: | Article |
|---|---|
| Additional Information: | Availability of data and materials: The gut metagenome shotgun sequencing data can be found at PRJNA1050903 and the saliva 16S rRNA gene amplicon sequencing data can be found at PRJNA1052073. Code for the analysis undertaken in R can be found at: https://github.com/nteng22/CALADRIO-paper. Funding Information: The CALADRIO Project received funding from Fundació Privada Institut d’Investigació Oncològica de Vall d’Hebron. This work was funded by BigC grant 17-16R to Hall LJ and Robinson SD (studentship for Teng NMY). Hall LJ and Robinson SD are also supported by the Biotechnology and Biological Sciences Research Council (BBSRC), Institute Strategic Programme Gut Microbes and Health BB/R012490/1, and its constituent projects BBS/E/F/000PR10353 and BBS/E/F/000PR10356. Hall LJ is also supported by Wellcome Trust Investigator Awards 100974/C/13/Z and 220876/Z/20/Z. Robinson T is supported by a National Institute for Health Research Development and Skills Enhancement Award (NIHR 302363). |
| Uncontrolled Keywords: | 16s rrna gene amplicon sequencing,breast cancer,eribulin,immunotherapy,metastatic breast cancer,microbiota,pembrolizumab,shotgun metagenomic sequencing,microbiology,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2400/2404 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School Faculty of Science > School of Biological Sciences |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging Faculty of Science > Research Groups > Cells and Tissues |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 07 Dec 2024 01:41 |
| Last Modified: | 13 Dec 2024 01:38 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/97941 |
| DOI: | 10.20517/mrr.2024.49 |
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