4.7 Review

Microbiota and their metabolites potentiate cancer immunotherapy: Therapeutic target or resource for small molecule drug discovery?

Journal

FRONTIERS IN PHARMACOLOGY
Volume 13, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2022.1091124

Keywords

microbiota; microbial metabolites; small molecule drugs; immune checkpoint inhibitors; immunotherapy response

Funding

  1. National Natural Science Foundation of China [82172634, 81902792]
  2. Key Program of the Science and Technology Bureau of Sichuan [2021YFSY0007]
  3. 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University [ZYYC20013]

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Microbiota is not only a target for drugs, but also a valuable resource for drug development. It plays a critical role in modulating the immune system and impacting the efficacy and toxicity of cancer immunotherapy. Utilizing microbiota or developing microbiota-derived medications can provide novel therapeutic strategies for overcoming resistance to cancer immunotherapy and immune-related adverse events.
Increasing evidence has proved that microbiota is not only the target of small molecule drugs but also an underexplored resource for developing small molecule drugs. Meanwhile, microbiota as a critical modulator of the immune system impacts the efficacy and toxicity of cancer immunotherapy. Harnessing microbiota or developing microbiota-derived medications provide novel therapeutic strategies to overcome resistance to cancer immunotherapy and immune-related adverse events (irAEs). In this review, we elucidate how microbiota and their metabolites impact anti-tumor immunity and immunotherapy efficacy and highlight the potential of microbiota and their metabolites as a resource for small molecule drug discovery. We further overview the current landscape of clinical trials evaluating the potential effect of microbiota and their metabolites on immunotherapy outcomes, presenting future trends in the field of microbiota-based therapies. Microbiota-based therapies are promising therapeutic options to promote therapeutic efficacy and diminish the toxicity of immunotherapy.

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