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Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis

Nature Medicine volume 24, pages 1804–1808 (2018)Cite this article

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An Author Correction to this article was published on 27 November 2018

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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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Fig. 1: Endoscopic changes and characterization of colonic mucosal infiltrate throughout clinical course.
Fig. 2: Microbiome analysis of patient and donor intestinal bacteria by 16S deep sequencing.

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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.

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.

Authors and 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

Authors
  1. Yinghong Wang
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  13. Gottumukkala S. Raju
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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.

Corresponding author

Correspondence to Yinghong Wang.

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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.

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Wang, Y., Wiesnoski, D.H., Helmink, B.A. et al. Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis. Nat Med 24, 1804–1808 (2018). https://doi.org/10.1038/s41591-018-0238-9

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