Abstract

We report the first case series of immune checkpoint inhibitors (ICI)-associated colitis successfully treated with fecal microbiota transplantation, with reconstitution of the gut microbiome and a relative increase in the proportion of regulatory T-cells within the colonic mucosa. These preliminary data provide evidence that modulation of the gut microbiome may abrogate ICI-associated colitis.

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Data availability

Patient-related data not included in the paper were generated as part of clinical trials and may be subject to patient confidentiality. Any data and materials that can be shared will be released via a Material Transfer Agreement. Sequence data has been deposited at the European Genome-phenome Archive (EGA), which is hosted by the EBI and the CRG, under accession number EGAS00001003217.

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Change history

  • 27 November 2018

    In the version of this article originally published, an author was missing from the author list. Alexander J. Lazar should have been included between Jorge M. Blando and James P. Allison. The author has been added to the list, and the author contributions section has been updated to include Alexander J. Lazar’s contribution to the study. The error has been corrected in the print, PDF and HTML versions of the manuscript.

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Acknowledgments

We are grateful for the following funding support: Andrew Sabin Family Fellows Program (private donation to J.A.W); MD Anderson Cancer Center’s Melanoma Moon Shot Program (grant no. 710499-80-111538-19, to J.A.W.); American Association for Cancer Research Stand Up to Cancer (grant no. SU2C-AACR-IRG-19-17, to J.A.W.); National Institutes of Health (grant no. R01 CA219896-01A1, to J.A.W.); National Institutes of Health (grant no. R01 HL124112, to R.R.J.); Cancer Prevention and Research Institute of Texas (grant no. RR160089, to R.R.J.).

Author information

Author notes

  1. These authors contributed equally: Yinghong Wang, Diana H. Wiesnoski, Beth A. Helmink.

  2. These authors jointly supervised this work: Jennifer A. Wargo, Robert R. Jenq.

Affiliations

  1. Department of Gastroenterology, Hepatology & Nutrition, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    • Yinghong Wang
    • , Hamzah Abu-Sbeih
    • , Gottumukkala S. Raju
    •  & John R. Stroehlein
  2. Department of Genomic Medicine, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    • Diana H. Wiesnoski
    • , Christopher A. Sanchez
    • , Chia-Chi Chang
    • , Alexander J. Lazar
    • , Jennifer A. Wargo
    •  & Robert R. Jenq
  3. Department of Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    • Beth A. Helmink
    • , Vancheswaran Gopalakrishnan
    •  & Jennifer A. Wargo
  4. Department of Internal Medicine, Baylor College of Medicine, Houston, TX, USA

    • Kati Choi
  5. Center for Infectious Diseases, School of Public Health, The University of Texas, Houston, TX, USA

    • Hebert L. DuPont
    •  & Zhi-Dong Jiang
  6. Kelsey Research Foundation, Houston, TX, USA

    • Hebert L. DuPont
  7. Department of Translational Molecular Pathology, Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    • Edwin R. Parra
    • , Alejandro Francisco-Cruz
    •  & Michael T. Tetzlaff
  8. Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    • Matthew T. Campbell
    • , Jianjun Gao
    • , Sumit K. Subudhi
    •  & Padmanee Sharma
  9. Department of Pathology, Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    • Dipen M. Maru
    • , Alexander J. Lazar
    •  & Michael T. Tetzlaff
  10. Department of Immunology, Division of Basic Science Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    • Jorge M. Blando
    • , James P. Allison
    •  & Padmanee Sharma
  11. Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    • Robert R. Jenq

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Contributions

Y.W. recruited and treated patients. Y.W., D.H.W., B.A.H., V.G., K.C., H.L.D., Z.-D.J., H.A.-S. C.A.S., C.-C.C., E.R.P., A.F.-C., G.S.R., J.R.S, M.T.C., J.G., S.K.S., D.M.M., J.M.B., A.J.L., J.P.A., P.S., M.T.T., J.A.W., and R.R.J. completed stool and tissue immunohistochemistry studies and analyzed/interpreted data. Y.W., B.A.H., V.G., M.T.T., J.A.W., and R.R.J. prepared the manuscript. All authors approved the manuscript.

Competing interests

J.A.W. and V.G. are inventors on a US patent application (PCT/US17/53,717) submitted by The University of Texas MD Anderson Cancer Center that covers methods to enhance checkpoint blockade therapy by the microbiome., J.A.W. is a paid speaker for Imedex, Dava Oncology, Omniprex, Illumina, Gilead, MedImmune and Bristol Meyers Squibb. J.A.W. is a consultant / advisory board member for Roche-Genentech, Novartis, Astra-Zeneca, Glaxo Smith Klein, Bristol Meyers Squibb, Merck, and Microbiome DX. J.A.W. also receives clinical trial support from Glaxo Smith Klein, Roche-Genentech, Bristol Meyers Squibb, and Novartis. V.G. is a consultant at Microbiome DX, and ExpertConnect. R.R.J. is on the scientific advisory board for Seres Therapeutics, Inc., has consulted for Ziopharm Oncology and Microbiome Dx, and holds patents licensed to Seres Therapeutics, Inc. M.T.T. serves on the advisory board for Novartis, Seattle Genetics, and Myriad Genetics. J.A.W., P.S., and J.P.A. are members of the Parker Institute for Cancer Immunotherapy at MD Anderson Cancer Center. P.S. is a consultant for Constellation, Kite Pharma, Neon, BioAtla, Pieris Pharmaceuticals, Oncolytics Biotech, Merck, BioMx, Forty-Seven, Polaris, Apricity, Marker Therapeutics, Codiak, Jounce Therapeutics, and is also a stockholder from Jounce Therapeutics, Neon, BioAtla, Forty-Seven, Apricity, Polaris, Marker Therapeutics, Codiak, and Kite Pharma. J.P.A. is a stockholder for Jounce Therapeutics, Neon, BioAtla, Forty-Seven, Apricity, Polaris, Marker Therapeutics, Codiak, and Kite Pharma. J.P.A. is also a consultant for Jounce Therapeutics, Neon, Amgen, Forty-Seven, Apricity, Polaris, Marker Therapeutics, Codiak, BioAlta LLC, and Tvardi Therapeutics. The other authors declare no competing interests.

Corresponding author

Correspondence to Yinghong Wang.

Supplementary information

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    Supplementary Figures 1–7, Supplementary Tables 1 and 2

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DOI

https://doi.org/10.1038/s41591-018-0238-9