Gut microbiota modulates adoptive cell therapy via CD8α dendritic cells and IL-12

JCI Insight
Mireia Uribe-HerranzAndrea Facciabene

Abstract

Adoptive T cell therapy (ACT) is a promising new modality for malignancies. Here, we report that adoptive T cell efficacy in tumor-bearing mice is significantly affected by differences in the native composition of the gut microbiome or treatment with antibiotics, or by heterologous fecal transfer. Depletion of bacteria with vancomycin decreased the rate of tumor growth in mice from The Jackson Laboratory receiving ACT, whereas treatment with neomycin and metronidazole had no effect, indicating the role of specific bacteria in host response. Vancomycin treatment induced an increase in systemic CD8α+ DCs, which sustained systemic adoptively transferred antitumor T cells in an IL-12-dependent manner. In subjects undergoing allogeneic hematopoietic cell transplantation, we found that oral vancomycin also increased IL-12 levels. Collectively, our findings demonstrate an important role played by the gut microbiota in the antitumor effectiveness of ACT and suggest potentially new avenues to improve response to ACT by altering the gut microbiota.

References

Sep 2, 1998·International Journal of Cancer. Journal International Du Cancer·H JiT C Wu
Jun 19, 2001·Current Opinion in Immunology·A Lanzavecchia, F Sallusto
Jan 17, 2003·The New England Journal of Medicine·Lin ZhangGeorge Coukos
Feb 4, 2003·Nature Reviews. Immunology·Giorgio Trinchieri
Apr 1, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Mark E DudleySteven A Rosenberg
Dec 8, 2005·Applied and Environmental Microbiology·Catherine Lozupone, Rob Knight
Oct 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Daniel J PowellSteven A Rosenberg
Jul 28, 2007·The Journal of Clinical Investigation·Chrystal M PaulosNicholas P Restifo
Dec 28, 2007·Infection and Immunity·Melissa BarmanNita Salzman
Apr 22, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Daisuke FujiwaraJonathan Braun
May 30, 2008·Nature·Sarkis K MazmanianDennis L Kasper
Jan 24, 2009·Immunological Reviews·Lyudmila LyakhFranca Gerosa
Mar 24, 2009·Current Opinion in Immunology·Steven A Rosenberg, Mark E Dudley
Oct 20, 2009·Cell·Ivaylo I IvanovDan R Littman
Nov 17, 2009·Bioinformatics·J Gregory CaporasoRob Knight
Dec 8, 2009·Journal of Autoimmunity·June L RoundSarkis K Mazmanian
Mar 3, 2010·Immunological Reviews·Ken Shortman, William R Heath
Mar 13, 2010·PloS One·Morgan N PriceAdam P Arkin
Apr 13, 2010·Nature Methods·J Gregory CaporasoRob Knight
Jun 23, 2010·Proceedings of the National Academy of Sciences of the United States of America·June L Round, Sarkis K Mazmanian
Aug 17, 2010·Bioinformatics·Robert C Edgar
Oct 5, 2010·Clinical & Developmental Immunology·Mingli XuTakayuki Yoshimoto
Jan 5, 2011·Scandinavian Journal of Infectious Diseases·Sriharsha RaoSidney Tessler
Jun 3, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Richard W JosephLaszlo G Radvanyi
Jul 1, 2011·Journal of Cancer·Mark E Dudley
Aug 13, 2011·The New England Journal of Medicine·David L PorterCarl H June
Feb 24, 2012·Gut Microbes·Hsin-Jung Wu, Eric Wu
Mar 23, 2012·Nature Reviews. Cancer·Karolina Palucka, Jacques Banchereau
Mar 23, 2012·Nature Reviews. Immunology·Nicholas P RestifoSteven A Rosenberg
Apr 6, 2012·PloS One·Camilla Hartmann Friis HansenAxel Kornerup Hansen

❮ Previous
Next ❯

Citations

Jun 5, 2019·International Journal of Molecular Sciences·Giovanni Brandi, Giorgio Frega
Apr 19, 2019·Journal for Immunotherapy of Cancer·Jessica FesslerThomas F Gajewski
Aug 31, 2019·Nature Reviews. Immunology·Stefanie K WculekDavid Sancho
Sep 10, 2020·Nature Reviews. Urology·Lisa Derosa, Laurence Zitvogel
Jun 16, 2018·World Journal of Gastroenterology : WJG·Romain VillégerMathilde Bonnet
Dec 13, 2019·Mediators of Inflammation·Carmine CarboneEmilio Bria
Mar 30, 2020·Protein & Cell·Qingjun LiuLigong Chen
Dec 10, 2019·The Journal of Clinical Investigation·Mireia Uribe-HerranzAndrea Facciabene
Jul 7, 2020·Frontiers in Immunology·Alba Rodriguez-GarciaSonia Guedan
Apr 4, 2019·Journal for Immunotherapy of Cancer·Muhammad Bilal Abid
May 11, 2019·Clinical & Translational Immunology·Sherly MardianaPhillip Kevin Darcy
Dec 13, 2019·Experimental Hematology & Oncology·Muhammad Bilal AbidParameswaran N Hari
Sep 20, 2019·International Journal of Molecular Sciences·Romain VillégerMathilde Bonnet
Jun 27, 2020·Stem Cell Research & Therapy·P Stephen PatrickTammy L Kalber
Feb 7, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Heather M McGeeWendy A Woodward
Jul 26, 2019·Life Sciences·Yalda HekmatshoarSepideh Zununi Vahed
Jan 14, 2021·Gut Microbes·Harry Cheuk Hay LauJun Yu
Nov 28, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Jia DongLiang Liu
Jun 25, 2020·Seminars in Cancer Biology·Raghwendra Pratap SinghRashmi Kumar
Jan 28, 2021·International Journal of Molecular Sciences·Mireia Uribe-HerranzCarlos Fernández de Larrea
Feb 5, 2019·The Lancet Oncology·Jennifer L McQuadeJennifer A Wargo
Nov 6, 2018·Trends in Immunology·Alexandria P CogdillJennifer A Wargo
Mar 2, 2021·Current Opinion in Immunology·Kathy D McCoy, Lukas F Mager
Mar 13, 2021·Frontiers in Immunology·Tejeshwar JainVikas Dudeja
May 25, 2021·The Journal of Pain : Official Journal of the American Pain Society·Emily PayneGlenn W Stevenson
Aug 21, 2021·BMC Cancer·Zi-Kun YuPei-Yu Huang
Aug 18, 2021·Cancer Discovery·Lisa DerosaLaurence Zitvogel

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
PCR
electrophoresis
ELISA

Software Mentioned

PyNAST
QIIME
FastTree
FlowJo
PERMANOVA
UCLUST

Related Concepts

Related Feeds

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Cancer Vaccines

Cancer vaccines are vaccines that either treat existing cancer or prevent development of a cancer.

Bacteriotherapy (ASM)

Bacteriotherapy, also known as fecal transplantation, involves the transfer of stool from a healthy donor into the gastrointestinal tract for the purpose of treating recurrent C. difficile colitis. Here is the latest on bacteriotherapy.

Bacteriotherapy

Bacteriotherapy, also known as fecal transplantation, involves the transfer of stool from a healthy donor into the gastrointestinal tract for the purpose of treating recurrent C. difficile colitis. Here is the latest on bacteriotherapy.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.