The role of HIF-1α in BCG-stimulated macrophages polarization and their tumoricidal effects in vitro

Med Microbiol Immunol. 2021 Jun;210(2-3):149-156. doi: 10.1007/s00430-021-00708-3. Epub 2021 May 11.

Abstract

BCG is widely used for cancer treatment, where macrophages play an important role. However, the mechanism of BCG affecting macrophages remains poorly understood. In this study, we used BCG to stimulate myeloid-derived macrophages lacking HIF-1α, the levels of TNF-α, IL-1β, CD86 of macrophages and their effects on the growth of tumor cells MCA207 and B16-F10 were detected. We found that the absence of HIF-1α prevents BCG-stimulated macrophages from polarizing towards the M (BCG) and attenuating its killing effect on tumor cells. In addition, we demonstrated that the tumors of mice lacking HIF-1α in macrophages were significantly increased by the experiment of mice transplantation. Our study provides relevant evidence for exploring the mechanism of the BCG vaccine in the prevention and treatment of related diseases.

Keywords: BCG; HIF-1α; Macrophages; Polarized; Tumor.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • B7-2 Antigen / metabolism
  • BCG Vaccine / pharmacology*
  • Cell Line, Tumor
  • Cytokines / metabolism*
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Interleukin-1beta / metabolism
  • Macrophage Activation*
  • Macrophages / drug effects*
  • Macrophages / physiology*
  • Mice
  • Mice, Knockout
  • Models, Animal
  • Neoplasm Transplantation
  • Neoplasms / therapy
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antineoplastic Agents
  • B7-2 Antigen
  • BCG Vaccine
  • Cytokines
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • IL1B protein, mouse
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha