Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy
Ayelet Sivan,Leticia Corrales,Nathaniel Hubert,Jason B. Williams,Keston Aquino-Michaels,Zachary M. Earley,Franco W. Benyamin,Yuk Man Lei,Bana Jabri,Maria-Luisa Alegre,Eugene B. Chang,Thomas F. Gajewski +11 more
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TLDR
Comparison of melanoma growth in mice harboring distinct commensal microbiota and observed differences in spontaneous antitumor immunity, suggests that manipulating the microbiota may modulate cancer immunotherapy.Abstract:
T cell infiltration of solid tumors is associated with favorable patient outcomes, yet the mechanisms underlying variable immune responses between individuals are not well understood. One possible modulator could be the intestinal microbiota. We compared melanoma growth in mice harboring distinct commensal microbiota and observed differences in spontaneous antitumor immunity, which were eliminated upon cohousing or after fecal transfer. Sequencing of the 16S ribosomal RNA identified Bifidobacterium as associated with the antitumor effects. Oral administration of Bifidobacterium alone improved tumor control to the same degree as programmed cell death protein 1 ligand 1 (PD-L1)–specific antibody therapy (checkpoint blockade), and combination treatment nearly abolished tumor outgrowth. Augmented dendritic cell function leading to enhanced CD8+ T cell priming and accumulation in the tumor microenvironment mediated the effect. Our data suggest that manipulating the microbiota may modulate cancer immunotherapy.read more
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Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors
Bertrand Routy,Bertrand Routy,Bertrand Routy,Lisa Derosa,Lisa Derosa,Lisa Derosa,Connie P.M. Duong,Connie P.M. Duong,Maryam Tidjani Alou,Maryam Tidjani Alou,Maryam Tidjani Alou,Romain Daillère,Romain Daillère,Romain Daillère,Aurélie Fluckiger,Aurélie Fluckiger,Meriem Messaoudene,Meriem Messaoudene,Conrad Rauber,Conrad Rauber,Conrad Rauber,Maria Paula Roberti,Maria Paula Roberti,Marine Fidelle,Marine Fidelle,Caroline Flament,Caroline Flament,Vichnou Poirier-Colame,Vichnou Poirier-Colame,Paule Opolon,Christophe Klein,Kristina Iribarren,Laura Mondragón,Nicolas Jacquelot,Nicolas Jacquelot,Nicolas Jacquelot,Bo Qu,Bo Qu,Bo Qu,Gladys Ferrere,Gladys Ferrere,Gladys Ferrere,Céline Clémenson,Céline Clémenson,Laura Mezquita,Jordi Remon Masip,C. Naltet,Solenn Brosseau,Coureche Kaderbhai,Corentin Richard,Hira Rizvi,Florence Levenez,Nathalie Galleron,Benoit Quinquis,Nicolas Pons,Bernhard Ryffel,Veronique Minard-Colin,Patrick Gonin,Jean-Charles Soria,Eric Deutsch,Eric Deutsch,Yohann Loriot,Yohann Loriot,François Ghiringhelli,Gérard Zalcman,François Goldwasser,B. Escudier,B. Escudier,Matthew D. Hellmann,Matthew D. Hellmann,Alexander M.M. Eggermont,Alexander M.M. Eggermont,Didier Raoult,Laurence Albiges,Laurence Albiges,Guido Kroemer,Laurence Zitvogel +76 more
TL;DR: It is found that primary resistance to ICIs can be attributed to abnormal gut microbiome composition, and Antibiotics inhibited the clinical benefit of ICIs in patients with advanced cancer.
Journal ArticleDOI
Elements of cancer immunity and the cancer–immune set point
Daniel S. Chen,Ira Mellman +1 more
TL;DR: Clinical studies are beginning to define these factors as immune profiles that can predict responses to immunotherapy, suggesting that a broader view of cancer immunity is required.
Journal ArticleDOI
Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy.
TL;DR: As the molecular mechanisms of resistance to immunotherapy are elucidated, actionable strategies to prevent or treat them may be derived to improve clinical outcomes for patients.
Journal ArticleDOI
Understanding the tumor immune microenvironment (TIME) for effective therapy.
Mikhail Binnewies,Edward W. Roberts,Kelly Kersten,Vincent Chan,Douglas F. Fearon,Miriam Merad,Lisa M. Coussens,Dmitry I. Gabrilovich,Suzanne Ostrand-Rosenberg,Suzanne Ostrand-Rosenberg,Catherine C. Hedrick,Robert H. Vonderheide,Mikael J. Pittet,Rakesh K. Jain,Weiping Zou,T. Kevin Howcroft,Elisa C. Woodhouse,Robert A. Weinberg,Matthew F. Krummel +18 more
TL;DR: By parsing the unique classes and subclasses of tumor immune microenvironment (TIME) that exist within a patient’s tumor, the ability to predict and guide immunotherapeutic responsiveness will improve, and new therapeutic targets will be revealed.
Journal ArticleDOI
Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients
Vancheswaran Gopalakrishnan,Vancheswaran Gopalakrishnan,Christine N. Spencer,Christine N. Spencer,Luigi Nezi,Alexandre Reuben,Miles C. Andrews,Tatiana Karpinets,Peter A. Prieto,D. Vicente,K. Hoffman,Spencer C. Wei,Alexandria P. Cogdill,Li Zhao,Courtney W. Hudgens,Diane S. Hutchinson,T. Manzo,M. Petaccia de Macedo,Tiziana Cotechini,T. Kumar,Wei Shen Chen,Sangeetha M. Reddy,R. Szczepaniak Sloane,Jessica Galloway-Peña,Hong Jiang,P. L. Chen,Elizabeth J. Shpall,Katayoun Rezvani,Amin M. Alousi,Roy F. Chemaly,Samuel A. Shelburne,Luis M Vence,Pablo C. Okhuysen,V. B. Jensen,Alton G. Swennes,Florencia McAllister,E. Marcelo Riquelme Sanchez,Yu Zhang,Laurence Zitvogel,Nicolas Pons,Jacob Austin-Breneman,Lauren E. Haydu,Elizabeth M. Burton,J. M. Gardner,E. Sirmans,Jing Shan Hu,Alexander J. Lazar,Takahiro Tsujikawa,Adi Diab,Hussein Abdul-Hassan Tawbi,Isabella C. Glitza,Wen-Jen Hwu,Sapna Pradyuman Patel,Scott E. Woodman,Rodabe N. Amaria,Michael A. Davies,Jeffrey E. Gershenwald,Patrick Hwu,J. E. Lee,Jianhua Zhang,Lisa M. Coussens,Zachary A. Cooper,P.A. Futreal,Carrie R. Daniel,Carrie R. Daniel,Nadim J. Ajami,Joseph F. Petrosino,Michael T. Tetzlaff,Pradeep Sharma,James P. Allison,Robert R. Jenq,Jennifer A. Wargo +71 more
TL;DR: Examination of the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients.
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