From nature to clinic: Quercetin's role in breast cancer immunomodulation

Front Immunol. 2024 Dec 6:15:1483459. doi: 10.3389/fimmu.2024.1483459. eCollection 2024.

Abstract

Immunotherapy has brought hope to many breast cancer patients, but not all patients benefit from it. Quercetin (Qu), a natural product found in various sources, has anti-inflammatory and anti-tumor properties. We conducted a review of the pharmacological research of Qu in regulating anti-tumor immunity in vivo and in vitro. Qu can directly regulate the local tumor microenvironment (TME) by enhancing the activity of immune cells which includes promoting the infiltration of T cells and natural killer (NK) cells, inhibiting the recruitment of myeloid-derived suppressor cells and tumor-associated macrophages. Additionally, Qu inhibits anaerobic glycolysis in tumor cells, thereby reducing the production and transport of lactic acid. It also suppresses tumor angiogenesis by targeting the vascular endothelial growth factor (VEGF) pathway and the vitamin D pathway. Furthermore, Qu can enhance the efficacy of immunotherapy for breast cancer by modulating the systemic microenvironment. This includes inhibiting obesity-related chronic inflammation to decrease the production of inflammatory factors, regulating the composition of intestinal microbiota, and intervening in the metabolism of intestinal flora. At the same time, we also address challenges in the clinical application of Qu, such as low absorption rates and unknown effective doses. In conclusion, we highlight Qu as a natural immunomodulator that enhances immune cell activity and has the potential to be developed as an adjunct for breast cancer.

Keywords: Quercetin; breast cancer; immunotherapy; natural immunomodulator; tumor immune microenvironment.

Publication types

  • Review

MeSH terms

  • Animals
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / immunology
  • Breast Neoplasms* / metabolism
  • Female
  • Humans
  • Immunomodulation* / drug effects
  • Immunotherapy / methods
  • Quercetin* / pharmacology
  • Quercetin* / therapeutic use
  • Tumor Microenvironment* / drug effects
  • Tumor Microenvironment* / immunology

Substances

  • Quercetin

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (No.82374178), the Natural Science Foundation of Shandong Province (NO.ZR2022MH180).