Autophagy inhibition induces the repolarisation of tumour-associated macrophages and enhances chemosensitivity of laryngeal cancer cells to cisplatin in mice

Cancer Immunol Immunother. 2019 Dec;68(12):1909-1920. doi: 10.1007/s00262-019-02415-8. Epub 2019 Oct 22.

Abstract

Tumour-associated macrophages (TAMs) are the key components in the tumour microenvironment. TAMs have two major subtypes, M1 and M2. M1 macrophages are tumour inhibitory, while M2 macrophages are tumour promotive. Repolarising TAMs from M2 to M1 is a promising strategy in cancer treatment. M1 and M2 macrophages were generated from murine bone marrow-derived macrophages (BMDMs). We found that chloroquine (CQ), an autophagy inhibitor, was able to repolarise M2 macrophages to the anti-tumour M1 phenotype. The repolarised macrophages demonstrated higher phagocytotic activity towards Hep-2 laryngeal tumour cells and re-sensitised Hep-2 cells to cisplatin (CDDP) treatment in vitro. While CQ did not demonstrate cytotoxicity to Hep-2 cells in vitro, CQ treatment reduced Hep-2 laryngeal tumour growth in vivo and improved CDDP treatment outcomes. It seems that CQ-induced M2-to-M1 macrophage repolarisation played an important role in tumour growth inhibition, and the CQ/CDDP combined therapy might have clinical potential in laryngeal cancer treatment.

Keywords: Autophagy inhibition; Chloroquine (CQ); Hep-2 laryngeal cancer; Macrophage repolarisation; Tumour-associated macrophages (TAMs).

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Autophagy
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transdifferentiation
  • Chloroquine / pharmacology
  • Cisplatin / therapeutic use*
  • Cytokines / metabolism
  • Drug Resistance, Neoplasm
  • Laryngeal Neoplasms / drug therapy
  • Laryngeal Neoplasms / immunology*
  • Macrophages / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Th1 Cells / immunology
  • Th2 Cells / immunology

Substances

  • Cytokines
  • Chloroquine
  • Cisplatin