Combined tumor-associated microbiome and immune gene expression profiling predict response to neoadjuvant chemo-radiotherapy in locally advanced rectal cancer
Locally advanced rectal cancer (LARC) is treated with neoadjuvant chemo-radiotherapy (nCRT) followed by surgery. A minority of patients show complete response (CR) to nCRT and may avoid surgery and its functional consequences. Instead, most patients show non-complete response (non-CR) and may benefi...
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Taylor & Francis Group
2025-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2465015 |
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| author | Raffaello Roesel Francesco Strati Camilla Basso Samantha Epistolio Paolo Spina Julija Djordjevic Elisa Sorrenti Martina Villa Agnese Cianfarani Francesco Mongelli Jacopo Galafassi Sotirios G. Popeskou Federica Facciotti Cecilia Caprera Federica Melle Pietro Edoardo Majno-Hurst Alessandra Franzetti-Pellanda Sara De Dosso Ferdinando Bonfiglio Milo Frattini Dimitrios Christoforidis Giandomenica Iezzi |
| author_facet | Raffaello Roesel Francesco Strati Camilla Basso Samantha Epistolio Paolo Spina Julija Djordjevic Elisa Sorrenti Martina Villa Agnese Cianfarani Francesco Mongelli Jacopo Galafassi Sotirios G. Popeskou Federica Facciotti Cecilia Caprera Federica Melle Pietro Edoardo Majno-Hurst Alessandra Franzetti-Pellanda Sara De Dosso Ferdinando Bonfiglio Milo Frattini Dimitrios Christoforidis Giandomenica Iezzi |
| author_sort | Raffaello Roesel |
| collection | DOAJ |
| description | Locally advanced rectal cancer (LARC) is treated with neoadjuvant chemo-radiotherapy (nCRT) followed by surgery. A minority of patients show complete response (CR) to nCRT and may avoid surgery and its functional consequences. Instead, most patients show non-complete response (non-CR) and may benefit from additional treatments to increase CR rates. Reliable predictive markers are lacking. Aim of this study was to identify novel signatures predicting nCRT responsiveness. We performed a combined analysis of tumor-associated microbiome and immune gene expression profiling of diagnostic biopsies from 70 patients undergoing nCRT followed by rectal resection, including 16 with CR and 54 with non-CR. Findings were validated by an independent cohort of 49 patients, including 7 with CR and 42 with non-CR. Intratumoral microbiota significantly differed between CR and non-CR groups at genus and species level. Colonization by bacterial species of Ruminococcus genera was consistently associated with CR, whereas abundance of Fusobacterium, Porhpyromonas, and Oscillibacter species predicted non-CR. Immune gene profiling revealed a panel of 59 differentially expressed genes and significant upregulation of IFN-gamma and -alpha response in patients with CR. Integrated microbiome and immune gene profiling analysis unraveled clustering of microbial taxa with each other and with immune cell-related genes and allowed the identification of a combined signature correctly identifying non-CRS in both cohorts. Thus, combined intratumoral microbiome-immune profiling improves the prediction of response to nCRT. Correct identification of unresponsive patients and of bacteria promoting responsiveness might lead to innovative therapeutic approaches based on gut microbiota pre-conditioning to increase nCRT effectiveness in LARC. |
| format | Article |
| id | doaj-art-5388bcf9fa2647be87c058e50e90bd04 |
| institution | DOAJ |
| issn | 2162-402X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-5388bcf9fa2647be87c058e50e90bd042025-08-20T03:12:31ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2025.2465015Combined tumor-associated microbiome and immune gene expression profiling predict response to neoadjuvant chemo-radiotherapy in locally advanced rectal cancerRaffaello Roesel0Francesco Strati1Camilla Basso2Samantha Epistolio3Paolo Spina4Julija Djordjevic5Elisa Sorrenti6Martina Villa7Agnese Cianfarani8Francesco Mongelli9Jacopo Galafassi10Sotirios G. Popeskou11Federica Facciotti12Cecilia Caprera13Federica Melle14Pietro Edoardo Majno-Hurst15Alessandra Franzetti-Pellanda16Sara De Dosso17Ferdinando Bonfiglio18Milo Frattini19Dimitrios Christoforidis20Giandomenica Iezzi21Department of Surgery, Ente Ospedaliero Cantonale, Lugano, SwitzerlandDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, ItalyLaboratory for Translational Surgical Research, Ente Ospedaliero Cantonale, Bellinzona, SwitzerlandLaboratory of Molecular Pathology, Institute of Pathology, Locarno, SwitzerlandLaboratory of Molecular Pathology, Institute of Pathology, Locarno, SwitzerlandLaboratory for Translational Surgical Research, Ente Ospedaliero Cantonale, Bellinzona, SwitzerlandLaboratory for Translational Surgical Research, Ente Ospedaliero Cantonale, Bellinzona, SwitzerlandLaboratory for Translational Surgical Research, Ente Ospedaliero Cantonale, Bellinzona, SwitzerlandDepartment of Surgery, Ente Ospedaliero Cantonale, Lugano, SwitzerlandDepartment of Surgery, Ente Ospedaliero Cantonale, Lugano, SwitzerlandDepartment of Surgery, Ente Ospedaliero Cantonale, Lugano, SwitzerlandDepartment of Surgery, Ente Ospedaliero Cantonale, Lugano, SwitzerlandDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, ItalyDivision of Hematopathology, IEO European Institute of Oncology IRCCS, Milan, ItalyDivision of Hematopathology, IEO European Institute of Oncology IRCCS, Milan, ItalyDepartment of Surgery, Ente Ospedaliero Cantonale, Lugano, SwitzerlandService of Radiotherapy, Gruppo Ospedaliero Moncucco, Clinica Moncucco, Lugano, SwitzerlandFaculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, SwitzerlandDepartment of Molecular Medicine and Medical Biotechnology, University of Naples, Naples, ItalyLaboratory of Molecular Pathology, Institute of Pathology, Locarno, SwitzerlandDepartment of Surgery, Ente Ospedaliero Cantonale, Lugano, SwitzerlandLaboratory for Translational Surgical Research, Ente Ospedaliero Cantonale, Bellinzona, SwitzerlandLocally advanced rectal cancer (LARC) is treated with neoadjuvant chemo-radiotherapy (nCRT) followed by surgery. A minority of patients show complete response (CR) to nCRT and may avoid surgery and its functional consequences. Instead, most patients show non-complete response (non-CR) and may benefit from additional treatments to increase CR rates. Reliable predictive markers are lacking. Aim of this study was to identify novel signatures predicting nCRT responsiveness. We performed a combined analysis of tumor-associated microbiome and immune gene expression profiling of diagnostic biopsies from 70 patients undergoing nCRT followed by rectal resection, including 16 with CR and 54 with non-CR. Findings were validated by an independent cohort of 49 patients, including 7 with CR and 42 with non-CR. Intratumoral microbiota significantly differed between CR and non-CR groups at genus and species level. Colonization by bacterial species of Ruminococcus genera was consistently associated with CR, whereas abundance of Fusobacterium, Porhpyromonas, and Oscillibacter species predicted non-CR. Immune gene profiling revealed a panel of 59 differentially expressed genes and significant upregulation of IFN-gamma and -alpha response in patients with CR. Integrated microbiome and immune gene profiling analysis unraveled clustering of microbial taxa with each other and with immune cell-related genes and allowed the identification of a combined signature correctly identifying non-CRS in both cohorts. Thus, combined intratumoral microbiome-immune profiling improves the prediction of response to nCRT. Correct identification of unresponsive patients and of bacteria promoting responsiveness might lead to innovative therapeutic approaches based on gut microbiota pre-conditioning to increase nCRT effectiveness in LARC.https://www.tandfonline.com/doi/10.1080/2162402X.2025.2465015Immune cell gene profilingintratumoral microbiotaLARCnCRTpredictive signature |
| spellingShingle | Raffaello Roesel Francesco Strati Camilla Basso Samantha Epistolio Paolo Spina Julija Djordjevic Elisa Sorrenti Martina Villa Agnese Cianfarani Francesco Mongelli Jacopo Galafassi Sotirios G. Popeskou Federica Facciotti Cecilia Caprera Federica Melle Pietro Edoardo Majno-Hurst Alessandra Franzetti-Pellanda Sara De Dosso Ferdinando Bonfiglio Milo Frattini Dimitrios Christoforidis Giandomenica Iezzi Combined tumor-associated microbiome and immune gene expression profiling predict response to neoadjuvant chemo-radiotherapy in locally advanced rectal cancer OncoImmunology Immune cell gene profiling intratumoral microbiota LARC nCRT predictive signature |
| title | Combined tumor-associated microbiome and immune gene expression profiling predict response to neoadjuvant chemo-radiotherapy in locally advanced rectal cancer |
| title_full | Combined tumor-associated microbiome and immune gene expression profiling predict response to neoadjuvant chemo-radiotherapy in locally advanced rectal cancer |
| title_fullStr | Combined tumor-associated microbiome and immune gene expression profiling predict response to neoadjuvant chemo-radiotherapy in locally advanced rectal cancer |
| title_full_unstemmed | Combined tumor-associated microbiome and immune gene expression profiling predict response to neoadjuvant chemo-radiotherapy in locally advanced rectal cancer |
| title_short | Combined tumor-associated microbiome and immune gene expression profiling predict response to neoadjuvant chemo-radiotherapy in locally advanced rectal cancer |
| title_sort | combined tumor associated microbiome and immune gene expression profiling predict response to neoadjuvant chemo radiotherapy in locally advanced rectal cancer |
| topic | Immune cell gene profiling intratumoral microbiota LARC nCRT predictive signature |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2465015 |
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