The Impact of the Fecal Microbiome on Cancer Immunotherapy
Recent advances in culture-free methods of studying the human microbiome, coupled with strong bioinformatics tools, have provided new insights on the role of the human microbiome in health and disease. The human gut, in particular, houses a vast number and diverse variety of microbes. A plethora of evidence has demonstrated the significant effects of the gut microbiome on local and systemic immunity. Studies in hematopoietic stem cell transplantation recipients provided early evidence of the involvement of the gut microbiome in the development of graft-versus-host disease and its related mortality. Cancer immunotherapy and checkpoint inhibitors, in particular, harness the power of the host’s immune system to fight a range of malignancies. Resistance to immunotherapy and fatal immune-related adverse events both continue to be challenges in the field. The role of the human gut microbiome in affecting the response to immunotherapy was recently uncovered through a series of preclinical and clinical studies. The evidence presented in these studies provides tremendous potential for gut microbes to be used for biomarker development and therapeutic intervention trials.
Compliance with Ethical Standards
Jason J. Luke has received the following funding: Department of Defense Career Development Award (W81XWH-17-1-0265), the Arthur J Schreiner Family Melanoma Research Fund, the J. Edward Mahoney Foundation Research Fund, Brush Family Immunotherapy Research Fund, and Buffet Fund for Cancer Immunotherapy.
Conflict of interest
Jason J. Luke declares the following: consultancy—7 Hills, Aduro, Actym, Alphamab Oncology, Amgen, Array, AstraZeneca, BeneVir, Bristol-Myers Squibb, Castle, CheckMate, Compugen, EMD Serono, Gilead, Ideaya, Janssen, Merck, NewLink, Novartis, RefleXion, Spring Bank, Syndax, Tempest, and WntRx; research support (all institutional except as marked)—AbbVie, Array (personal), Boston Biomedical, Bristol-Myers Squibb, Celldex, CheckMate (personal), Corvus, Delcath, Evelo (personal), Five Prime, Genentech, Immunocore, Incyte, MedImmune, Macrogenics, Novartis, Pharmacyclics, Palleon (personal), Merck, Tesaro, and Xencor; travel—Amgen, Array, AstraZeneca, BeneVir, Bristol-Myers Squibb, Castle, CheckMate, EMD Serono, Gilead, Ideaya, Janssen, Merck, NewLink, Novartis, and RefleXion. Patents: Jason J. Luke is a co-inventor on a patent submitted by the University of Chicago covering use of microbiota to improve cancer immunotherapy outcomes. Afaf E.G. Osman declares that she has no conflicts of interest that might be relevant to the contents of this manuscript.
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