Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome

Lisa Derosa; Valerio Iebba; Carolina Alves Costa Silva; Gianmarco Piccinno; Guojun Wu; Leonardo Lordello; Bertrand Routy; Naisi Zhao; Cassandra Thelemaque; Roxanne Birebent; Federica Marmorino; Marine Fidelle; Meriem Messaoudene; Andrew Maltez Thomas; Gerard Zalcman; Sylvie Friard; Julien Mazieres; Clarisse Audigier-Valette; Denis Moro Sibilot; François Goldwasser; Arnaud Scherpereel; Hervé Pegliasco; François Ghiringhelli; Nicole Bouchard; Cissé Sow; Ines Darik; Silvia Zoppi; Pierre Ly; Anna Reni; Romain Daillère; Eric Deutsch; Karla A. Lee; Laura A. Bolte; Johannes R. Björk; Rinse K. Weersma; Fabrice Barlesi; Lucas Padilha; Ana Finzel; Morten L. Isaksen; Bernard Escudier; Laurence Albiges; David Planchard; Fabrice André; Chiara Cremolini; Stéphanie Martinez; Benjamin Besse; Liping Zhao; Nicola Segata; Jérôme Wojcik; Guido Kroemer; Laurence Zitvogel

doi:10.1016/j.cell.2024.05.029

Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome

Lisa Derosa, Valerio Iebba, Carolina Alves Costa Silva, Gianmarco Piccinno, Guojun Wu, Leonardo Lordello, Bertrand Routy, Naisi Zhao, Cassandra Thelemaque, Roxanne Birebent, Federica Marmorino, Marine Fidelle, Meriem Messaoudene, Andrew Maltez Thomas, Gerard Zalcman, Sylvie Friard, Julien Mazieres, Clarisse Audigier-Valette, Denis Moro Sibilot, François GoldwasserArnaud Scherpereel, Hervé Pegliasco, François Ghiringhelli, Nicole Bouchard, Cissé Sow, Ines Darik, Silvia Zoppi, Pierre Ly, Anna Reni, Romain Daillère, Eric Deutsch, Karla A. Lee, Laura A. Bolte, Johannes R. Björk, Rinse K. Weersma, Fabrice Barlesi, Lucas Padilha, Ana Finzel, Morten L. Isaksen, Bernard Escudier, Laurence Albiges, David Planchard, Fabrice André, Chiara Cremolini, Stéphanie Martinez, Benjamin Besse, Liping Zhao, Nicola Segata, Jérôme Wojcik, Guido Kroemer, Laurence Zitvogel

Research output: Contribution to journal › Article › peer-review

61 Scopus citations

Abstract

The gut microbiota influences the clinical responses of cancer patients to immunecheckpoint inhibitors (ICIs). However, there is no consensus definition of detrimental dysbiosis. Based on metagenomics (MG) sequencing of 245 non-small cell lung cancer (NSCLC) patient feces, we constructed species-level co-abundance networks that were clustered into species-interacting groups (SIGs) correlating with overall survival. Thirty-seven and forty-five MG species (MGSs) were associated with resistance (SIG1) and response (SIG2) to ICIs, respectively. When combined with the quantification of Akkermansia species, this procedure allowed a person-based calculation of a topological score (TOPOSCORE) that was validated in an additional 254 NSCLC patients and in 216 genitourinary cancer patients. Finally, this TOPOSCORE was translated into a 21-bacterial probe set-based qPCR scoring that was validated in a prospective cohort of NSCLC patients as well as in colorectal and melanoma patients. This approach could represent a dynamic diagnosis tool for intestinal dysbiosis to guide personalized microbiota-centered interventions.

Original language	English (US)
Pages (from-to)	3373-3389.e16
Journal	Cell
Volume	187
Issue number	13
DOIs	https://doi.org/10.1016/j.cell.2024.05.029
State	Published - Jun 20 2024
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Biochemistry, Genetics and Molecular Biology

Keywords

Akkermansia muciniphila
PD-(L)1
TOPOSCORE
biomarker
cancer
gut microbiota
immune-checkpoint blockade
immunotherapy
metagenomics
microbiome

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10.1016/j.cell.2024.05.029

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Derosa, L., Iebba, V., Silva, C. A. C., Piccinno, G., Wu, G., Lordello, L., Routy, B., Zhao, N., Thelemaque, C., Birebent, R., Marmorino, F., Fidelle, M., Messaoudene, M., Thomas, A. M., Zalcman, G., Friard, S., Mazieres, J., Audigier-Valette, C., Sibilot, D. M., ... Zitvogel, L. (2024). Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome. Cell, 187(13), 3373-3389.e16. https://doi.org/10.1016/j.cell.2024.05.029

@article{db5fc74b16e74a028531a816042a4c88,

title = "Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome",

abstract = "The gut microbiota influences the clinical responses of cancer patients to immunecheckpoint inhibitors (ICIs). However, there is no consensus definition of detrimental dysbiosis. Based on metagenomics (MG) sequencing of 245 non-small cell lung cancer (NSCLC) patient feces, we constructed species-level co-abundance networks that were clustered into species-interacting groups (SIGs) correlating with overall survival. Thirty-seven and forty-five MG species (MGSs) were associated with resistance (SIG1) and response (SIG2) to ICIs, respectively. When combined with the quantification of Akkermansia species, this procedure allowed a person-based calculation of a topological score (TOPOSCORE) that was validated in an additional 254 NSCLC patients and in 216 genitourinary cancer patients. Finally, this TOPOSCORE was translated into a 21-bacterial probe set-based qPCR scoring that was validated in a prospective cohort of NSCLC patients as well as in colorectal and melanoma patients. This approach could represent a dynamic diagnosis tool for intestinal dysbiosis to guide personalized microbiota-centered interventions.",

keywords = "Akkermansia muciniphila, PD-(L)1, TOPOSCORE, biomarker, cancer, gut microbiota, immune-checkpoint blockade, immunotherapy, metagenomics, microbiome",

author = "Lisa Derosa and Valerio Iebba and Silva, {Carolina Alves Costa} and Gianmarco Piccinno and Guojun Wu and Leonardo Lordello and Bertrand Routy and Naisi Zhao and Cassandra Thelemaque and Roxanne Birebent and Federica Marmorino and Marine Fidelle and Meriem Messaoudene and Thomas, {Andrew Maltez} and Gerard Zalcman and Sylvie Friard and Julien Mazieres and Clarisse Audigier-Valette and Sibilot, {Denis Moro} and Fran{\c c}ois Goldwasser and Arnaud Scherpereel and Herv{\'e} Pegliasco and Fran{\c c}ois Ghiringhelli and Nicole Bouchard and Ciss{\'e} Sow and Ines Darik and Silvia Zoppi and Pierre Ly and Anna Reni and Romain Daill{\`e}re and Eric Deutsch and Lee, {Karla A.} and Bolte, {Laura A.} and Bj{\"o}rk, {Johannes R.} and Weersma, {Rinse K.} and Fabrice Barlesi and Lucas Padilha and Ana Finzel and Isaksen, {Morten L.} and Bernard Escudier and Laurence Albiges and David Planchard and Fabrice Andr{\'e} and Chiara Cremolini and St{\'e}phanie Martinez and Benjamin Besse and Liping Zhao and Nicola Segata and J{\'e}r{\^o}me Wojcik and Guido Kroemer and Laurence Zitvogel",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s)",

year = "2024",

month = jun,

day = "20",

doi = "10.1016/j.cell.2024.05.029",

language = "English (US)",

volume = "187",

pages = "3373--3389.e16",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "13",

}

Derosa, L, Iebba, V, Silva, CAC, Piccinno, G, Wu, G, Lordello, L, Routy, B, Zhao, N, Thelemaque, C, Birebent, R, Marmorino, F, Fidelle, M, Messaoudene, M, Thomas, AM, Zalcman, G, Friard, S, Mazieres, J, Audigier-Valette, C, Sibilot, DM, Goldwasser, F, Scherpereel, A, Pegliasco, H, Ghiringhelli, F, Bouchard, N, Sow, C, Darik, I, Zoppi, S, Ly, P, Reni, A, Daillère, R, Deutsch, E, Lee, KA, Bolte, LA, Björk, JR, Weersma, RK, Barlesi, F, Padilha, L, Finzel, A, Isaksen, ML, Escudier, B, Albiges, L, Planchard, D, André, F, Cremolini, C, Martinez, S, Besse, B, Zhao, L, Segata, N, Wojcik, J, Kroemer, G & Zitvogel, L 2024, 'Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome', Cell, vol. 187, no. 13, pp. 3373-3389.e16. https://doi.org/10.1016/j.cell.2024.05.029

TY - JOUR

T1 - Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome

AU - Derosa, Lisa

AU - Iebba, Valerio

AU - Silva, Carolina Alves Costa

AU - Piccinno, Gianmarco

AU - Wu, Guojun

AU - Lordello, Leonardo

AU - Routy, Bertrand

AU - Zhao, Naisi

AU - Thelemaque, Cassandra

AU - Birebent, Roxanne

AU - Marmorino, Federica

AU - Fidelle, Marine

AU - Messaoudene, Meriem

AU - Thomas, Andrew Maltez

AU - Zalcman, Gerard

AU - Friard, Sylvie

AU - Mazieres, Julien

AU - Audigier-Valette, Clarisse

AU - Sibilot, Denis Moro

AU - Goldwasser, François

AU - Scherpereel, Arnaud

AU - Pegliasco, Hervé

AU - Ghiringhelli, François

AU - Bouchard, Nicole

AU - Sow, Cissé

AU - Darik, Ines

AU - Zoppi, Silvia

AU - Ly, Pierre

AU - Reni, Anna

AU - Daillère, Romain

AU - Deutsch, Eric

AU - Lee, Karla A.

AU - Bolte, Laura A.

AU - Björk, Johannes R.

AU - Weersma, Rinse K.

AU - Barlesi, Fabrice

AU - Padilha, Lucas

AU - Finzel, Ana

AU - Isaksen, Morten L.

AU - Escudier, Bernard

AU - Albiges, Laurence

AU - Planchard, David

AU - André, Fabrice

AU - Cremolini, Chiara

AU - Martinez, Stéphanie

AU - Besse, Benjamin

AU - Zhao, Liping

AU - Segata, Nicola

AU - Wojcik, Jérôme

AU - Kroemer, Guido

AU - Zitvogel, Laurence

PY - 2024/6/20

Y1 - 2024/6/20

N2 - The gut microbiota influences the clinical responses of cancer patients to immunecheckpoint inhibitors (ICIs). However, there is no consensus definition of detrimental dysbiosis. Based on metagenomics (MG) sequencing of 245 non-small cell lung cancer (NSCLC) patient feces, we constructed species-level co-abundance networks that were clustered into species-interacting groups (SIGs) correlating with overall survival. Thirty-seven and forty-five MG species (MGSs) were associated with resistance (SIG1) and response (SIG2) to ICIs, respectively. When combined with the quantification of Akkermansia species, this procedure allowed a person-based calculation of a topological score (TOPOSCORE) that was validated in an additional 254 NSCLC patients and in 216 genitourinary cancer patients. Finally, this TOPOSCORE was translated into a 21-bacterial probe set-based qPCR scoring that was validated in a prospective cohort of NSCLC patients as well as in colorectal and melanoma patients. This approach could represent a dynamic diagnosis tool for intestinal dysbiosis to guide personalized microbiota-centered interventions.

AB - The gut microbiota influences the clinical responses of cancer patients to immunecheckpoint inhibitors (ICIs). However, there is no consensus definition of detrimental dysbiosis. Based on metagenomics (MG) sequencing of 245 non-small cell lung cancer (NSCLC) patient feces, we constructed species-level co-abundance networks that were clustered into species-interacting groups (SIGs) correlating with overall survival. Thirty-seven and forty-five MG species (MGSs) were associated with resistance (SIG1) and response (SIG2) to ICIs, respectively. When combined with the quantification of Akkermansia species, this procedure allowed a person-based calculation of a topological score (TOPOSCORE) that was validated in an additional 254 NSCLC patients and in 216 genitourinary cancer patients. Finally, this TOPOSCORE was translated into a 21-bacterial probe set-based qPCR scoring that was validated in a prospective cohort of NSCLC patients as well as in colorectal and melanoma patients. This approach could represent a dynamic diagnosis tool for intestinal dysbiosis to guide personalized microbiota-centered interventions.

KW - Akkermansia muciniphila

KW - PD-(L)1

KW - TOPOSCORE

KW - biomarker

KW - cancer

KW - gut microbiota

KW - immune-checkpoint blockade

KW - immunotherapy

KW - metagenomics

KW - microbiome

UR - http://www.scopus.com/inward/record.url?scp=85195850162&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85195850162&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2024.05.029

DO - 10.1016/j.cell.2024.05.029

M3 - Article

C2 - 38906102

AN - SCOPUS:85195850162

SN - 0092-8674

VL - 187

SP - 3373-3389.e16

JO - Cell

JF - Cell

IS - 13

ER -

Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome

Abstract

All Science Journal Classification (ASJC) codes

Keywords

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