Commensal bacteria and fungi differentially regulate tumor responses to radiation therapy

Cancer Cell. 2021 Sep 13;39(9):1202-1213.e6. doi: 10.1016/j.ccell.2021.07.002. Epub 2021 Jul 29.


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.

Keywords: T cells; bacteria; dectin-1; fungi; immunotherapy; macrophages; microbiome; mycobiome; radiation; tumor immunology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifungal Agents / administration & dosage*
  • Antifungal Agents / pharmacology
  • Bacteria / classification*
  • Bacteria / immunology
  • Breast Neoplasms / immunology
  • Breast Neoplasms / microbiology
  • Breast Neoplasms / therapy*
  • Combined Modality Therapy
  • Down-Regulation
  • Female
  • Fungi / classification
  • Fungi / drug effects*
  • Fungi / immunology
  • Gastrointestinal Microbiome / drug effects
  • Gastrointestinal Microbiome / radiation effects
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Humans
  • Lectins, C-Type / genetics*
  • Melanoma / immunology
  • Melanoma / microbiology
  • Melanoma / therapy*
  • Mice
  • Symbiosis
  • T-Lymphocytes / metabolism
  • Tumor-Associated Macrophages / metabolism
  • Up-Regulation / drug effects
  • Up-Regulation / radiation effects
  • Xenograft Model Antitumor Assays


  • Antifungal Agents
  • CLEC7A protein, human
  • Lectins, C-Type