4.8 Article

Commensal bacteria and fungi differentially regulate tumor responses to radiation therapy

Journal

CANCER CELL
Volume 39, Issue 9, Pages 1202-+

Publisher

CELL PRESS
DOI: 10.1016/j.ccell.2021.07.002

Keywords

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Funding

  1. National Cancer Institute, NIH [CA191139, CA220000]
  2. American Society for Radiation Oncology
  3. National Institute of Diabetes and Digestive and Kidney Diseases, NIH [DK093496]
  4. Janis and William Wetsman Family Chair in Inflammatory Bowel Disease Research

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Studies have shown that intestinal fungi play a role in regulating antitumor immune responses following radiation in mouse models of breast cancer and melanoma. Fungi and bacteria have opposite influences on these responses, with depletion of fungi enhancing responsiveness to radiation while depletion of bacteria reducing responsiveness. Elevated intratumoral expression of Dectin-1, a primary innate sensor of fungi, is negatively associated with survival in breast cancer patients.
Studies suggest that the efficacy of cancer chemotherapy and immunotherapy is influenced by intestinal bacteria. However, the influence of the microbiome on radiation therapy is not as well understood, and the microbiome comprises more than bacteria. Here, we find that intestinal fungi regulate antitumor immune responses following radiation in mouse models of breast cancer and melanoma and that fungi and bacteria have opposite influences on these responses. Antibiotic-mediated depletion or gnotobiotic exclusion of fungi enhances responsiveness to radiation, whereas antibiotic-mediated depletion of bacteria reduces responsiveness and is associated with overgrowth of commensal fungi. Further, elevated intratumoral expression of Dectin-1, a primary innate sensor of fungi, is negatively associated with survival in patients with breast cancer and is required for the effects of commensal fungi in mouse models of radiation therapy.

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