TY - JOUR
T1 - Longitudinal gut microbiome changes in immune checkpoint blockade-treated advanced melanoma
AU - Björk, Johannes R
AU - Bolte, Laura A
AU - Maltez Thomas, Andrew
AU - Lee, Karla A
AU - Rossi, Niccolo
AU - Wind, Thijs T
AU - Smit, Lotte M
AU - Armanini, Federica
AU - Asnicar, Francesco
AU - Blanco-Miguez, Aitor
AU - Board, Ruth
AU - Calbet-Llopart, Neus
AU - Derosa, Lisa
AU - Dhomen, Nathalie
AU - Brooks, Kelly
AU - Harland, Mark
AU - Harries, Mark
AU - Lorigan, Paul
AU - Manghi, Paolo
AU - Marais, Richard
AU - Newton-Bishop, Julia
AU - Nezi, Luigi
AU - Pinto, Federica
AU - Potrony, Miriam
AU - Puig, Susana
AU - Serra-Bellver, Patricio
AU - Shaw, Heather M
AU - Tamburini, Sabrina
AU - Valpione, Sara
AU - Waldron, Levi
AU - Zitvogel, Laurence
AU - Zolfo, Moreno
AU - de Vries, Elisabeth G E
AU - Nathan, Paul
AU - Fehrmann, Rudolf S N
AU - Spector, Tim D
AU - Bataille, Véronique
AU - Segata, Nicola
AU - Hospers, Geke A P
AU - Weersma, Rinse K
N1 - © 2024. The Author(s).
PY - 2024/3/1
Y1 - 2024/3/1
N2 - Multiple clinical trials targeting the gut microbiome are being conducted to optimize treatment outcomes for immune checkpoint blockade (ICB). To improve the success of these interventions, understanding gut microbiome changes during ICB is urgently needed. Here through longitudinal microbiome profiling of 175 patients treated with ICB for advanced melanoma, we show that several microbial species-level genome bins (SGBs) and pathways exhibit distinct patterns from baseline in patients achieving progression-free survival (PFS) of 12 months or longer (PFS ≥12) versus patients with PFS shorter than 12 months (PFS <12). Out of 99 SGBs that could discriminate between these two groups, 20 were differentially abundant only at baseline, while 42 were differentially abundant only after treatment initiation. We identify five and four SGBs that had consistently higher abundances in patients with PFS ≥12 and <12 months, respectively. Constructing a log ratio of these SGBs, we find an association with overall survival. Finally, we find different microbial dynamics in different clinical contexts including the type of ICB regimen, development of immune-related adverse events and concomitant medication use. Insights into the longitudinal dynamics of the gut microbiome in association with host factors and treatment regimens will be critical for guiding rational microbiome-targeted therapies aimed at enhancing ICB efficacy.
AB - Multiple clinical trials targeting the gut microbiome are being conducted to optimize treatment outcomes for immune checkpoint blockade (ICB). To improve the success of these interventions, understanding gut microbiome changes during ICB is urgently needed. Here through longitudinal microbiome profiling of 175 patients treated with ICB for advanced melanoma, we show that several microbial species-level genome bins (SGBs) and pathways exhibit distinct patterns from baseline in patients achieving progression-free survival (PFS) of 12 months or longer (PFS ≥12) versus patients with PFS shorter than 12 months (PFS <12). Out of 99 SGBs that could discriminate between these two groups, 20 were differentially abundant only at baseline, while 42 were differentially abundant only after treatment initiation. We identify five and four SGBs that had consistently higher abundances in patients with PFS ≥12 and <12 months, respectively. Constructing a log ratio of these SGBs, we find an association with overall survival. Finally, we find different microbial dynamics in different clinical contexts including the type of ICB regimen, development of immune-related adverse events and concomitant medication use. Insights into the longitudinal dynamics of the gut microbiome in association with host factors and treatment regimens will be critical for guiding rational microbiome-targeted therapies aimed at enhancing ICB efficacy.
KW - Cognition
KW - Gastrointestinal Microbiome/genetics
KW - Humans
KW - Immune Checkpoint Inhibitors/therapeutic use
KW - Melanoma/drug therapy
KW - Microbiota
UR - http://www.scopus.com/inward/record.url?scp=85185094886&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/cca58027-1d22-382b-a0ba-3fac36680ec3/
U2 - 10.1038/s41591-024-02803-3
DO - 10.1038/s41591-024-02803-3
M3 - Article
C2 - 38365950
SN - 1078-8956
VL - 30
SP - 785
EP - 796
JO - Nature Medicine
JF - Nature Medicine
IS - 3
ER -