Profiling the gut and oral microbiota of hormone receptor-positive, HER2-negative metastatic breast cancer patients receiving pembrolizumab and eribulin
Year: 2024
Type: article
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.
Source: Microbiome Research Reports
DOI: 10.20517/mrr.2024.49
Authors: Nancy MY Teng, Andrea Malfettone, Matthew J Dalby, Raymond Kiu, David Seki, Tim Robinson, María Gion, Begoña Bermejo, José Manuel Pérez-García, Aleix Prat, Raúl Márquez Vázquez, Antonio Llombart-Cussac, Giuseppe Curigliano, Peter Schmid, Romualdo Barroso-Sousa, Mario Mancino, Eileen Shimizu, Jose Rodríguez-Morató, Leonardo Mina, Lindsay J Hall, Stephen D Robinson, Javier Cortés
Institutions: Quadram Institute, MedSIR (Spain), University of Birmingham, Technical University of Munich, University of Bristol, Hospital Universitario Ramón y Cajal, Universitat de València, Hospital Clínico Universitario de Valencia, INCLIVA Health Research Institute, Centro de Investigación Biomédica en Red de Cáncer, Hospital Clínic de Barcelona, MD Anderson Cancer Center Madrid, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, Hospital Arnau de Vilanova, University of Milan, European Institute of Oncology, Queen Mary University of London, Barts Cancer Institute, Hospital Sírio-Libanês, University of East Anglia, Universidad Europea de Madrid
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W4403953776