Skip to Main content Skip to Navigation
Journal articles

Gut microbiota signatures are associated with toxicity to combined CTLA-4 and PD-1 blockade

Miles Andrews 1, 2, 3 Connie Duong 4, 5, 6, 7 Vancheswaran Gopalakrishnan 1, 7 Valerio Iebba 4, 5, 7 Wei-Shen Chen 1, 8, 7 Lisa Derosa 5, 4, 6, 7 Md Abdul Wadud Khan 1, 7 Alexandria Cogdill 5, 6, 1, 7 Michael White 1, 7 Matthew Wong 1, 7 Gladys Ferrere 5, 4, 6, 7 Aurélie Fluckiger 5, 4, 6, 7 Maria Roberti 5, 4, 6, 7 Paule Opolon 4, 7 Maryam Tidjani Alou 5, 4, 6, 7 Satoru Yonekura 5, 4, 6, 7 Whijae Roh 1, 7 Christine Spencer 9, 7 Irina Fernandez Curbelo 1, 7 Luis Vence 1, 7 Alexandre Reuben 1, 7 Sarah Johnson 1, 7 Reetakshi Arora 1, 7 Golnaz Morad 1, 7 Matthew Lastrapes 1, 7 Erez Baruch 1, 7 Latasha Little 1, 7 Curtis Gumbs 1, 7 Zachary Cooper 10, 7 Peter Prieto 11, 7 Khalida Wani 1, 7 Alexander Lazar 1, 7 Michael Tetzlaff 1, 7 Courtney Hudgens 1, 7 Margaret Callahan 9, 12, 7 Matthew Adamow 12, 7 Michael Postow 12, 7 Charlotte Ariyan 12, 7 Pierre-Olivier Gaudreau 1, 7 Luigi Nezi 13, 7 Didier Raoult 14, 15, 7 Catalin Mihalcioiu 16, 7 Arielle Elkrief 16, 7 Rossanna Pezo 17, 7 Lauren Haydu 1, 7 Julie Simon 1, 7 Hussein Tawbi 1, 7 Jennifer Mcquade 1, 7 Patrick Hwu 1, 7 Wen-Jen Hwu 1, 7 Rodabe Amaria 1, 7 Elizabeth Burton 1 Scott Woodman 1 Stephanie Watowich 1 Adi Diab 1 Sapna Patel 1 Isabella Glitza 1 Michael Wong 1 Li Zhao 1 Jianhua Zhang 1 Nadim Ajami 1 Joseph Petrosino 18 Robert Jenq 1 Michael Davies 1 Jeffrey Gershenwald 1 P. Andrew Futreal 1 Padmanee Sharma 1 James Allison 1 Bertrand Routy 5, 4, 6, 7 Laurence Zitvogel 7, 4, 5, 6 Jennifer Wargo 1
Abstract : Treatment with combined immune checkpoint blockade (CICB) targeting CTLA-4 and PD-1 is associated with clinical benefit across tumor types, but also a high rate of immune-related adverse events. Insights into biomarkers and mechanisms of response and toxicity to CICB are needed. To address this, we profiled the blood, tumor and gut microbiome of 77 patients with advanced melanoma treated with CICB, with a high rate of any ≥grade 3 immune-related adverse events (49%) with parallel studies in pre-clinical models. Tumor-associated immune and genomic biomarkers of response to CICB were similar to those identified for ICB monotherapy, and toxicity from CICB was associated with a more diverse peripheral T-cell repertoire. Profiling of gut microbiota demonstrated a significantly higher abundance of Bacteroides intestinalis in patients with toxicity, with upregulation of mucosal IL-1β in patient samples of colitis and in pre-clinical models. Together, these data offer potential new therapeutic angles for targeting toxicity to CICB.
Complete list of metadata

https://hal-amu.archives-ouvertes.fr/hal-03333724
Contributor : Isabelle Combe Connect in order to contact the contributor
Submitted on : Monday, September 6, 2021 - 1:30:18 PM
Last modification on : Tuesday, October 19, 2021 - 10:50:36 PM

File

2f0091ab-846d-4b59-9960-dcea2f...
Publication funded by an institution

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Collections

Citation

Miles Andrews, Connie Duong, Vancheswaran Gopalakrishnan, Valerio Iebba, Wei-Shen Chen, et al.. Gut microbiota signatures are associated with toxicity to combined CTLA-4 and PD-1 blockade. Nature Medicine, Nature Publishing Group, 2021, 27 (8), pp.1432-1441. ⟨10.1038/s41591-021-01406-6⟩. ⟨hal-03333724⟩

Share

Metrics

Record views

64

Files downloads

455