Association of gut microbiota and immune gene expression with response to targeted therapy in BRAF mutated melanoma
Abstract Gut microbiota has been associated with carcinogenesis and immune regulation. While there is evidence supporting its influence on immunotherapy response in melanoma, its impact on BRAF/MEK-targeted therapy remains unexplored. This study assessed gut microbiota composition and immune-associa...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-11054-2 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849763770537082880 |
|---|---|
| author | Mora Guardamagna Miguel-Angel Berciano-Guerrero Rocío Lavado-Valenzuela Édouard Auclin Juan Luis Onieva-Zafra Isaac Plaza-Andrades Javier Oliver Alicia Garrido-Aranda Elisabeth Perez-Ruiz Martina Álvarez María Carmen Ocaña María Isabel Queipo-Ortuño Isabel Barragán Antonio Rueda-Dominguez |
| author_facet | Mora Guardamagna Miguel-Angel Berciano-Guerrero Rocío Lavado-Valenzuela Édouard Auclin Juan Luis Onieva-Zafra Isaac Plaza-Andrades Javier Oliver Alicia Garrido-Aranda Elisabeth Perez-Ruiz Martina Álvarez María Carmen Ocaña María Isabel Queipo-Ortuño Isabel Barragán Antonio Rueda-Dominguez |
| author_sort | Mora Guardamagna |
| collection | DOAJ |
| description | Abstract Gut microbiota has been associated with carcinogenesis and immune regulation. While there is evidence supporting its influence on immunotherapy response in melanoma, its impact on BRAF/MEK-targeted therapy remains unexplored. This study assessed gut microbiota composition and immune-associated genes in melanoma, to generate hypothesis on prognostic and predictive biomarkers for BRAF/MEK inhibitor therapy. This prospective, observational study analyzed fecal and blood samples from 26 patients diagnosed with BRAF-mutated metastatic melanoma. Samples were collected at baseline (T0) and at first radiological evaluation (T1). Patients were stratified by treatment response and toxicity. Partial responders had baseline enrichment of Lachnospiraceae, Coriobacteriaceae, and Adlercreutzia. Complete responders showed abundance of Prevotellaceae, Cerasicoccaceae and Lawsonia. Oscillospira was associated with moderate-to-severe toxicity. Gene expression analysis revealed upregulation of TAP1 y PSMB8 during treatment in responders, with persistent downregulation of LAG3, CD36, SLAMF7, NOD1, SLAMF6, CX3CR1 and ICAM2. Overall, baseline microbiota composition differed by response depth, with abundance of Lachnospiraceae, Coriobacteriaceae, and Adlercreutzia in partial responders and Prevotellaceae, Cerasicoccaceae, and Lawsonia in complete responders. A gene signature of immune-suppresive genes was persistently downregulated in responders. Our findings suggest that specific gut microbial taxa and immune-related gene expression patterns may be associated with differential responses to BRAF/MEK-targeted therapy in metastatic melanoma. |
| format | Article |
| id | doaj-art-dae1b56df3ef4584a476a28d291381e6 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-dae1b56df3ef4584a476a28d291381e62025-08-20T03:05:18ZengNature PortfolioScientific Reports2045-23222025-07-0115111410.1038/s41598-025-11054-2Association of gut microbiota and immune gene expression with response to targeted therapy in BRAF mutated melanomaMora Guardamagna0Miguel-Angel Berciano-Guerrero1Rocío Lavado-Valenzuela2Édouard Auclin3Juan Luis Onieva-Zafra4Isaac Plaza-Andrades5Javier Oliver6Alicia Garrido-Aranda7Elisabeth Perez-Ruiz8Martina Álvarez9María Carmen Ocaña10María Isabel Queipo-Ortuño11Isabel Barragán12Antonio Rueda-Dominguez13Virgen de la Victoria University Hospital, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONANDDepartment of Medicine and Dermatology, Medical School University of MálagaVirgen de la Victoria University Hospital, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONANDInstitut BergoniéGroup of Translational Research in Cancer Immunotherapy and Epigenetics (B-05), Medical Oncology Unit of Virgen de la Victoria Hospital, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina–IBIMA Plataforma BionandVirgen de la Victoria University Hospital, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONANDVirgen de la Victoria University Hospital, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONANDVirgen de la Victoria University Hospital, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONANDGroup of “New Horizons for Cancer Patients” (B-23). Regional University Hospital, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONANDCancer Molecular Biology Laboratory, CIMESCancer Molecular Biology Laboratory, CIMESVirgen de la Victoria University Hospital, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONANDGroup of Pharmacoepigenetics, Department of Physiology and Pharmacology, Karolinska InstituteVirgen de la Victoria University Hospital, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONANDAbstract Gut microbiota has been associated with carcinogenesis and immune regulation. While there is evidence supporting its influence on immunotherapy response in melanoma, its impact on BRAF/MEK-targeted therapy remains unexplored. This study assessed gut microbiota composition and immune-associated genes in melanoma, to generate hypothesis on prognostic and predictive biomarkers for BRAF/MEK inhibitor therapy. This prospective, observational study analyzed fecal and blood samples from 26 patients diagnosed with BRAF-mutated metastatic melanoma. Samples were collected at baseline (T0) and at first radiological evaluation (T1). Patients were stratified by treatment response and toxicity. Partial responders had baseline enrichment of Lachnospiraceae, Coriobacteriaceae, and Adlercreutzia. Complete responders showed abundance of Prevotellaceae, Cerasicoccaceae and Lawsonia. Oscillospira was associated with moderate-to-severe toxicity. Gene expression analysis revealed upregulation of TAP1 y PSMB8 during treatment in responders, with persistent downregulation of LAG3, CD36, SLAMF7, NOD1, SLAMF6, CX3CR1 and ICAM2. Overall, baseline microbiota composition differed by response depth, with abundance of Lachnospiraceae, Coriobacteriaceae, and Adlercreutzia in partial responders and Prevotellaceae, Cerasicoccaceae, and Lawsonia in complete responders. A gene signature of immune-suppresive genes was persistently downregulated in responders. Our findings suggest that specific gut microbial taxa and immune-related gene expression patterns may be associated with differential responses to BRAF/MEK-targeted therapy in metastatic melanoma.https://doi.org/10.1038/s41598-025-11054-2Gut microbiotaMetastatic melanomaImmune expression genesTranslational researchBRAF mutated melanomaImmune system |
| spellingShingle | Mora Guardamagna Miguel-Angel Berciano-Guerrero Rocío Lavado-Valenzuela Édouard Auclin Juan Luis Onieva-Zafra Isaac Plaza-Andrades Javier Oliver Alicia Garrido-Aranda Elisabeth Perez-Ruiz Martina Álvarez María Carmen Ocaña María Isabel Queipo-Ortuño Isabel Barragán Antonio Rueda-Dominguez Association of gut microbiota and immune gene expression with response to targeted therapy in BRAF mutated melanoma Scientific Reports Gut microbiota Metastatic melanoma Immune expression genes Translational research BRAF mutated melanoma Immune system |
| title | Association of gut microbiota and immune gene expression with response to targeted therapy in BRAF mutated melanoma |
| title_full | Association of gut microbiota and immune gene expression with response to targeted therapy in BRAF mutated melanoma |
| title_fullStr | Association of gut microbiota and immune gene expression with response to targeted therapy in BRAF mutated melanoma |
| title_full_unstemmed | Association of gut microbiota and immune gene expression with response to targeted therapy in BRAF mutated melanoma |
| title_short | Association of gut microbiota and immune gene expression with response to targeted therapy in BRAF mutated melanoma |
| title_sort | association of gut microbiota and immune gene expression with response to targeted therapy in braf mutated melanoma |
| topic | Gut microbiota Metastatic melanoma Immune expression genes Translational research BRAF mutated melanoma Immune system |
| url | https://doi.org/10.1038/s41598-025-11054-2 |
| work_keys_str_mv | AT moraguardamagna associationofgutmicrobiotaandimmunegeneexpressionwithresponsetotargetedtherapyinbrafmutatedmelanoma AT miguelangelbercianoguerrero associationofgutmicrobiotaandimmunegeneexpressionwithresponsetotargetedtherapyinbrafmutatedmelanoma AT rociolavadovalenzuela associationofgutmicrobiotaandimmunegeneexpressionwithresponsetotargetedtherapyinbrafmutatedmelanoma AT edouardauclin associationofgutmicrobiotaandimmunegeneexpressionwithresponsetotargetedtherapyinbrafmutatedmelanoma AT juanluisonievazafra associationofgutmicrobiotaandimmunegeneexpressionwithresponsetotargetedtherapyinbrafmutatedmelanoma AT isaacplazaandrades associationofgutmicrobiotaandimmunegeneexpressionwithresponsetotargetedtherapyinbrafmutatedmelanoma AT javieroliver associationofgutmicrobiotaandimmunegeneexpressionwithresponsetotargetedtherapyinbrafmutatedmelanoma AT aliciagarridoaranda associationofgutmicrobiotaandimmunegeneexpressionwithresponsetotargetedtherapyinbrafmutatedmelanoma AT elisabethperezruiz associationofgutmicrobiotaandimmunegeneexpressionwithresponsetotargetedtherapyinbrafmutatedmelanoma AT martinaalvarez associationofgutmicrobiotaandimmunegeneexpressionwithresponsetotargetedtherapyinbrafmutatedmelanoma AT mariacarmenocana associationofgutmicrobiotaandimmunegeneexpressionwithresponsetotargetedtherapyinbrafmutatedmelanoma AT mariaisabelqueipoortuno associationofgutmicrobiotaandimmunegeneexpressionwithresponsetotargetedtherapyinbrafmutatedmelanoma AT isabelbarragan associationofgutmicrobiotaandimmunegeneexpressionwithresponsetotargetedtherapyinbrafmutatedmelanoma AT antonioruedadominguez associationofgutmicrobiotaandimmunegeneexpressionwithresponsetotargetedtherapyinbrafmutatedmelanoma |