Obesity correlates with the immunosuppressive ILC2s-MDSCs axis in advanced breast cancer

Immun Inflamm Dis. 2024 Mar;12(3):e1196. doi: 10.1002/iid3.1196.

Abstract

Aim: We investigated the relationship between the group 2 innate lymphoid cells (ILC2s)-myeloid-derived suppressor cells (MDSCs) axis and obesity-related breast cancer.

Methods: Fifty-eight patients with breast cancer who had first relapse and metastasis between January 2019 and August 2021 were enrolled. The proportions of ILC2s and MDSCs in blood and the levels of cytokines in serum were detected with flow cytometry. Correlation analysis among clinical characteristics (such as body mass index [BMI]), cytokines, ILC2s, and MDSCs was conducted.

Results: There was a significant difference in the proportions of ILC2s and MDSCs between the high BMI group and the normal BMI group (p < .05). In the triple-negative breast cancer (TNBC) patients, the proportions of ILC2s and MDSCs in the obese group were significantly higher than those in the nonobese group (p < .05). In all breast cancer patients, there was a positive correlation between BMI and the ILC2s-MDSCs axis (p < .05). However, there was no correlation observed between the number of metastases, progression-free survival, and the ILC2s-MDSCs axis (p > .05). Additionally, ILC2s showed positive correlations with MDSCs, interleukin-5 (IL-5), IL-10, IL-17A, (PD-L1), programmed cell death 2 ligand 2 (PD-L2), and molecular typing (p < .05). Similarly, MDSCs exhibited positive correlations with IL-5, IL-8, IL-9, IL-17A, PD-L1, and PD-L2 (p < .05). In patients with TNBC, there was a positive correlation between BMI and IL-5 (p < .05).

Conclusion: Conclusively, obesity may enhance the immunosuppressive effect of the ILC2-MDSC axis in advanced breast cancer. IL-5 may play a vital role in the ILC2-MDSC axis and obesity in TNBC.

Keywords: advanced breast cancer; group 2 innate lymphoid cells; inflammatory factors; interleukin; myeloid-derived suppressor cells; obesity.

MeSH terms

  • B7-H1 Antigen / metabolism
  • Cytokines / metabolism
  • Humans
  • Immunity, Innate
  • Interleukin-17 / metabolism
  • Interleukin-5 / metabolism
  • Lymphocytes / metabolism
  • Myeloid-Derived Suppressor Cells* / metabolism
  • Triple Negative Breast Neoplasms* / metabolism

Substances

  • B7-H1 Antigen
  • Interleukin-17
  • Interleukin-5
  • Cytokines