4.7 Article

Facts and Hopes for Gut Microbiota Interventions in Cancer Immunotherapy

Journal

CLINICAL CANCER RESEARCH
Volume 28, Issue 20, Pages 4370-4384

Publisher

AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-21-1129

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Funding

  1. NIH/NCI
  2. James W. and Frances G. McGlothlin Chair in Melanoma Immunotherapy Research
  3. [R01CA222203]
  4. [R01CA257265]
  5. [P50CA257265]

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The gut microbiome plays a significant role in immune checkpoint inhibitor therapy, and optimizing microbiota composition may improve immunotherapy outcomes.
Immune checkpoint inhibitors (ICI) targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) proteins transformed the management of advanced cancers. Many tumor-intrinsic factors modulate immunological and clinical responses to such therapies, but ample evidence also implicates the gut microbiome in responses. The gut microbiome, comprising the bacteria, archaea, fungi, and viruses that live in the human digestive tract, is an established determinant of host immunity, but its impact on response to ICI therapy in mice and humans with cancer has only recently been appreciated. Therapeutic interventions to optimize microbiota composition to improve immunotherapy outcomes show promise in mice and humans with cancer. In this review, we discuss the rationale for gut microbiome-based cancer therapies, the results from early-phase clinical trials, and possible future developments.

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