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Review
. 2023 Nov;29(11):897-911.
doi: 10.1016/j.molmed.2023.08.004. Epub 2023 Sep 11.

Manipulating the gut and tumor microbiota for immune checkpoint inhibitor therapy: from dream to reality

Nicolas Guillot  1 , Barnabé Roméo  1 , Shima Sepehri Manesh  1 , Gerard Milano  2 , Patrick Brest  1 , Laurence Zitvogel  3 , Paul Hofman  4 , Baharia Mograbi  5
Affiliations
Review

Manipulating the gut and tumor microbiota for immune checkpoint inhibitor therapy: from dream to reality

Nicolas Guillot et al. Trends Mol Med. 2023 Nov.

Abstract

The past decade has witnessed a revolution in cancer treatment by shifting from conventional therapies to immune checkpoint inhibitors (ICIs). These immunotherapies unleash the host immune system against the tumor and have achieved unprecedented durable remission. However, 80% of patients do not respond. This review discusses how bacteria are unexpected drivers that reprogram tumor immunity. Manipulating the microbiota impacts on tumor development and reprograms the tumor microenvironment (TME) of mice on immunotherapy. We anticipate that harnessing commensals and the tumor microbiome holds promise to identify patients who will benefit from immunotherapy and guide the choice of new ICI combinations to advance treatment efficacy.

Keywords: antibiotics; commensal; fecal microbiota transplantation; immune checkpoint inhibitor therapy; predictive biomarker; probiotics; tumor microbiota.

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Conflict of interest statement

Declaration of interests G.M. has received honoraria from MERCK and Bristol Myers Squibb (BMS) for lectures on this topic. P.H. has received honoraria from AstraZeneca, BMS, MSD, Lilly, Bayer, Pfizer, ThermoFisher Scientific, Roche, Illumina, Novartis, Biocartis, Janssen, Qiagen, and AbbVie for lectures, consulting fees, and advisory board membership. L.Z. has held research contracts with GSK, Incyte, Lytix, Kaleido, Innovate Pharma, Daiichi Sankyo, Pilege, Merus, Transgene, 9 m, Tusk, and Roche. L.Z. was on the Board of Directors of Transgene, is a cofounder of EverImmune, and holds patents covering the treatment of cancer and the therapeutic manipulation of the microbiota. N.G., B.R., S.S.M., P.B., and B.M. declare no conflicts of interest.

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