Gut microbiotas and immune checkpoint inhibitor therapy response: a causal or coincidental relationship?

Sok-Ja Janket 1 , Leland K. Ackerson 2  and Eleftherios P. Diamandis 3 , 4 , 5 , 6
  • 1 Translational Oral Medicine Section, Forsyth Institute, MA, Cambridge, USA
  • 2 Department of Public Health, University of Massachusetts at Lowell, MA, Lowell, USA
  • 3 Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, ON, Toronto, Canada
  • 4 Department of Laboratory Medicine and Pathobiology, University of Toronto, ON, Toronto, Canada
  • 5 Department of Clinical Biochemistry, University Health Network, ON, Toronto, Canada
  • 6 Head of Clinical Biochemistry, Mount Sinai Hospital and University Health Network, Toronto, Canada
Sok-Ja Janket, Leland K. Ackerson
  • Department of Public Health, University of Massachusetts at Lowell, Lowell, MA, USA
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and Eleftherios P. Diamandis
  • Corresponding author
  • Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada
  • Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
  • Department of Clinical Biochemistry, University Health Network, Toronto, ON, Canada
  • Head of Clinical Biochemistry, Mount Sinai Hospital and University Health Network, Toronto, Canada
  • Email
  • Search for other articles:
  • degruyter.comGoogle Scholar

Abstract

As the largest immune organ, human gut microbiome could influence the efficacy of immune checkpoint inhibitor therapy (ICI). However, identifying contributory microbes from over 35,000 species is virtually impossible and the identified microbes are not consistent among studies. The reason for the disparity may be that the microbes found in feces are markers of other factors that link immune response and microbiotas. Notably, gut microbiome is influenced by stool consistency, diet and other lifestyle factors. Therefore, the ICI and microbiotas relationship must be adjusted for potential confounders and analyzed longitudinally. Moreover, a recent study where 11 low-abundance commensal bacteria induced interferon-γ-producing CD8 T cells, challenges the validity of the abundance-oriented microbiotas investigations. This study also confirmed the hierarchy in immunogenic roles among microbiotas. Fecal transplantation trials in germ-free mice provided “the proof of principle” that germ-free mice reproduce the donor’s microbiome and corresponding ICI efficacy. However, species-specific biological differences prevent direct extrapolation between the results in murine and human models. Fecal transplantation or supplementation with microbes found in ICI responders requires caution due to potential adverse events.

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Clinical Chemistry and Laboratory Medicine ( CCLM) publishes articles on novel teaching and training methods applicable to laboratory medicine. CCLM welcomes contributions on the progress in fundamental and applied research and cutting-edge clinical laboratory medicine. It is one of the leading journals in the field, with an impact factor of over three. CCLM is the official journal of nine national clinical societies and associated with EFLM.

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