Macrophages reduce the sensitivity of osteosarcoma to neoadjuvant chemotherapy drugs by secreting Interleukin-1 beta

Cancer Lett. 2020 Jun 28:480:4-14. doi: 10.1016/j.canlet.2020.03.019. Epub 2020 Mar 24.

Abstract

Osteosarcoma is a common, highly malignant tumor of the musculoskeletal system in young people. Compared with simple amputation in the past, the application of neoadjuvant chemotherapy significantly improved the 5-year survival rate and limb-salvage rate of tumor patients without metastasis. However, the survival rate of patients with metastatic disease treated with neoadjuvant chemotherapy has remained stagnant over the past 30 years despite repeated attempts of adding neoadjuvant chemotherapy agents into the regimen or enhancing the chemotherapy drug dose. In this study, we revealed that macrophages, stimulated by neoadjuvant chemotherapy agents, could reduce the sensitivity of osteosarcoma cells to the drugs. Furthermore, we found that this phenomenon was strongly related to the secretion of the interleukin-1beta by macrophages. Our findings may provide new ideas for improving the efficiency of neoadjuvant chemotherapy for osteosarcoma.

Keywords: Drug sensitivity; Interleukin-1 beta; Neoadjuvant chemotherapy; Tumor-associated inflammatory environment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antineoplastic Agents / pharmacology
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / pathology
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Female
  • Humans
  • Interleukin-1 Receptor Accessory Protein / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism*
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Male
  • Mice, Inbred BALB C
  • Neoadjuvant Therapy
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / pathology
  • Receptors, Interleukin-1 Type I / metabolism
  • Tumor Microenvironment / drug effects
  • Xenograft Model Antitumor Assays
  • Young Adult

Substances

  • Antineoplastic Agents
  • IL1B protein, human
  • IL1R1 protein, human
  • IL1RAP protein, human
  • Interleukin-1 Receptor Accessory Protein
  • Interleukin-1beta
  • Receptors, Interleukin-1 Type I
  • Cisplatin