A mechanism of IL-34-induced resistance against cytotoxic anti-cancer therapies such as radiation by X-ray and chemotherapy by Oxaliplatin

Oncoimmunology. 2023 Jul 24;12(1):2238499. doi: 10.1080/2162402X.2023.2238499. eCollection 2023.

Abstract

Interleukin-34 (IL-34) has been known as a factor that is involved with tumor progression and therapeutic resistance. However, there are limitations to addressing the mechanism of how IL-34 induces therapeutic resistance. Here, we show a mechanism of IL-34-induced resistance against cytotoxic anti-cancer therapies such as radiotherapy using X-ray and chemotherapy by Oxaliplatin. This research demonstrates that IL-34 immunologically changes the tumor microenvironment after treatments with radiation or chemotherapeutic agents such as oxaliplatin. We identified the changes in immune cells using flow cytometry and immunofluorescent (IF) staining, which are up-regulated upon the existence of IL-34. Overall, these findings demonstrate the possibility of IL-34 blockade as a novel combination therapy for cancer.

Keywords: Chemotherapy; IL-34; immunosuppression; radiotherapy; therapeutic resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Drug Resistance, Neoplasm
  • Humans
  • Interleukins*
  • Neoplasms* / drug therapy
  • Neoplasms* / radiotherapy
  • Oxaliplatin / pharmacology
  • Oxaliplatin / therapeutic use
  • Radiation Tolerance
  • Tumor Microenvironment
  • X-Rays

Substances

  • Antineoplastic Agents
  • Interleukins
  • Oxaliplatin
  • IL34 protein, human

Grants and funding

This work was partly supported by research grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (#22K19449, K. Seino), Joint Research Program of the Institute for Genetic Medicine (K. Seino), the project of junior scientist promotion (K. Seino), and the Photo-excitonix Project in Hokkaido University (K. Seino).