Identification of dynamic microbiota signatures in patients with melanoma receiving icis: opportunities and challenges

Identification of dynamic microbiota signatures in patients with melanoma receiving icis: opportunities and challenges

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The composition of the gut microbiota has emerged as a tumour-extrinsic factor that modulates response to immune-checkpoint inhibitors (ICIs), although the lack of consistency in microbiota signatures across studies has limited their value as reliable biomarkers. Herein, we discuss a recent study in which longitudinal microbiome profiling identified several taxa that are persistently enriched in patients with melanoma and a favourable response to ICIs. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value online-access subscription $29.99 / 30 days cancel any time Learn more Subscribe to this journal Receive 12 print issues and online access $209.00 per year only $17.42 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES * Routy, B. et al. Melanoma and microbiota: current understanding and future directions. _Cancer Cell_ 42, 16–34 (2024). Article  CAS  PubMed  Google Scholar  * Davar, D. et al. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. _Science_ 371, 595–602 (2021). Article  CAS  PubMed  PubMed Central  Google Scholar  * Routy, B. et al. Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial. _Nat. Med._ 29, 2121–2132 (2023). Article  CAS  PubMed  Google Scholar  * Björk, J. R. et al. Longitudinal gut microbiome changes in immune checkpoint blockade-treated advanced melanoma. _Nat. Med._ https://doi.org/10.1038/s41591-024-02803-3 (2024). Article  PubMed  PubMed Central  Google Scholar  * Luu, M. et al. Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer. _Nat. Commun._ 12, 4077 (2021). Article  CAS  PubMed  PubMed Central  Google Scholar  * McCulloch, J. A. et al. Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1. _Nat. Med._ 28, 545–556 (2022). Article  CAS  PubMed  PubMed Central  Google Scholar  * Derosa, L. et al. Friendly-user score assessing gut dysbiosis and resistance to immune checkpoint inhibitors (ICI). _J. Clin. Oncol._ 41, 103 (2023). Article  Google Scholar  * Dizman, N. et al. Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial. _Nat. Med._ 28, 704–712 (2022). Article  CAS  PubMed  PubMed Central  Google Scholar  * Tanoue, T. et al. A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. _Nature_ 565, 600–605 (2019). Article  CAS  PubMed  Google Scholar  * Spreafico, A. et al. First-in-class Microbial Ecosystem Therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors (MET4-IO trial). _Ann. Oncol._ 34, 520–530 (2023). Article  CAS  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS S.M.V. is supported by a salary award from the Ontario Institute of Cancer Research and grants from the Hecht Family Foundation and Weston Foundation. D.D. is supported by grants from the Department of Defense (ME230254), Gateway Foundation for Cancer Research and National Institute of Health (P50 CA254865 (Project 2), R01 CA257265 and U01 CA271407). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Oncology, Western University, London, Ontario, Canada Saman Maleki Vareki * Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada Saman Maleki Vareki * Verspeeten Family Cancer Centre, Lawson Health Research Institute, London, Ontario, Canada Saman Maleki Vareki * Division of Medical Oncology, University of Pittsburgh, Pittsburgh, PA, USA Diwakar Davar * UPMC Hillman Cancer Center, Pittsburgh, PA, USA Diwakar Davar Authors * Saman Maleki Vareki View author publications You can also search for this author inPubMed Google Scholar * Diwakar Davar View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Diwakar Davar. ETHICS DECLARATIONS COMPETING INTERESTS S.M.V. is an independent director at IMV, and a consultant for Fed Bio and Kanvas Biosciences. D.D. receives institutional grants and research support from Arcus, Immunocore, Merck, Regeneron Pharmaceuticals and Tesaro/GSK; is a consultant for ACM Bio, Ascendis, Castle, Clinical Care Options, Gerson Lehrman Group, Immunitas, Medical Learning Group, Replimmune, Trisalus and Xilio Therapeutics; a member of the speakers’ bureau for Castle Biosciences; and is involved in the US Patent 63/124,231 (‘Compositions and Methods for Treating Cancer’) and US Patent 63/208,719 (‘Compositions and Methods For Responsiveness to Immune Checkpoint Inhibitors (ICI), Increasing Effectiveness of ICI and Treating Cancer’). RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Maleki Vareki, S., Davar, D. Identification of dynamic microbiota signatures in patients with melanoma receiving ICIs: opportunities and challenges. _Nat Rev Clin Oncol_ 21, 405–406 (2024). https://doi.org/10.1038/s41571-024-00882-2 Download citation * Published: 20 March 2024 * Issue Date: June 2024 * DOI: https://doi.org/10.1038/s41571-024-00882-2 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative

The composition of the gut microbiota has emerged as a tumour-extrinsic factor that modulates response to immune-checkpoint inhibitors (ICIs), although the lack of consistency in microbiota


signatures across studies has limited their value as reliable biomarkers. Herein, we discuss a recent study in which longitudinal microbiome profiling identified several taxa that are


persistently enriched in patients with melanoma and a favourable response to ICIs. Access through your institution Buy or subscribe This is a preview of subscription content, access via your


institution ACCESS OPTIONS Access through your institution Access Nature and 54 other Nature Portfolio journals Get Nature+, our best-value online-access subscription $29.99 / 30 days


cancel any time Learn more Subscribe to this journal Receive 12 print issues and online access $209.00 per year only $17.42 per issue Learn more Buy this article * Purchase on SpringerLink *


Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional


subscriptions * Read our FAQs * Contact customer support REFERENCES * Routy, B. et al. Melanoma and microbiota: current understanding and future directions. _Cancer Cell_ 42, 16–34 (2024).


Article  CAS  PubMed  Google Scholar  * Davar, D. et al. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. _Science_ 371, 595–602 (2021). Article 


CAS  PubMed  PubMed Central  Google Scholar  * Routy, B. et al. Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial. _Nat. Med._ 29, 2121–2132


(2023). Article  CAS  PubMed  Google Scholar  * Björk, J. R. et al. Longitudinal gut microbiome changes in immune checkpoint blockade-treated advanced melanoma. _Nat. Med._


https://doi.org/10.1038/s41591-024-02803-3 (2024). Article  PubMed  PubMed Central  Google Scholar  * Luu, M. et al. Microbial short-chain fatty acids modulate CD8+ T cell responses and


improve adoptive immunotherapy for cancer. _Nat. Commun._ 12, 4077 (2021). Article  CAS  PubMed  PubMed Central  Google Scholar  * McCulloch, J. A. et al. Intestinal microbiota signatures of


clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1. _Nat. Med._ 28, 545–556 (2022). Article  CAS  PubMed  PubMed Central  Google Scholar  *


Derosa, L. et al. Friendly-user score assessing gut dysbiosis and resistance to immune checkpoint inhibitors (ICI). _J. Clin. Oncol._ 41, 103 (2023). Article  Google Scholar  * Dizman, N. et


al. Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial. _Nat. Med._ 28, 704–712 (2022). Article  CAS 


PubMed  PubMed Central  Google Scholar  * Tanoue, T. et al. A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. _Nature_ 565, 600–605 (2019). Article  CAS  PubMed 


Google Scholar  * Spreafico, A. et al. First-in-class Microbial Ecosystem Therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors


(MET4-IO trial). _Ann. Oncol._ 34, 520–530 (2023). Article  CAS  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS S.M.V. is supported by a salary award from the Ontario Institute


of Cancer Research and grants from the Hecht Family Foundation and Weston Foundation. D.D. is supported by grants from the Department of Defense (ME230254), Gateway Foundation for Cancer


Research and National Institute of Health (P50 CA254865 (Project 2), R01 CA257265 and U01 CA271407). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Oncology, Western University,


London, Ontario, Canada Saman Maleki Vareki * Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada Saman Maleki Vareki * Verspeeten Family Cancer


Centre, Lawson Health Research Institute, London, Ontario, Canada Saman Maleki Vareki * Division of Medical Oncology, University of Pittsburgh, Pittsburgh, PA, USA Diwakar Davar * UPMC


Hillman Cancer Center, Pittsburgh, PA, USA Diwakar Davar Authors * Saman Maleki Vareki View author publications You can also search for this author inPubMed Google Scholar * Diwakar Davar


View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Diwakar Davar. ETHICS DECLARATIONS COMPETING INTERESTS S.M.V. is


an independent director at IMV, and a consultant for Fed Bio and Kanvas Biosciences. D.D. receives institutional grants and research support from Arcus, Immunocore, Merck, Regeneron


Pharmaceuticals and Tesaro/GSK; is a consultant for ACM Bio, Ascendis, Castle, Clinical Care Options, Gerson Lehrman Group, Immunitas, Medical Learning Group, Replimmune, Trisalus and Xilio


Therapeutics; a member of the speakers’ bureau for Castle Biosciences; and is involved in the US Patent 63/124,231 (‘Compositions and Methods for Treating Cancer’) and US Patent 63/208,719


(‘Compositions and Methods For Responsiveness to Immune Checkpoint Inhibitors (ICI), Increasing Effectiveness of ICI and Treating Cancer’). RIGHTS AND PERMISSIONS Reprints and permissions


ABOUT THIS ARTICLE CITE THIS ARTICLE Maleki Vareki, S., Davar, D. Identification of dynamic microbiota signatures in patients with melanoma receiving ICIs: opportunities and challenges. _Nat


Rev Clin Oncol_ 21, 405–406 (2024). https://doi.org/10.1038/s41571-024-00882-2 Download citation * Published: 20 March 2024 * Issue Date: June 2024 * DOI:


https://doi.org/10.1038/s41571-024-00882-2 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not


currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative