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

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

Acknowledgments

We thank all other members of Immunobiology laboratory for suggestions and technical assistance.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions:

NH, HW, and KS designed the study. NH and TK performed experiments. All authors analyzed data and discussed the results. NH, HW, TK, RO, KS contributed to manuscript preparation. All authors reviewed the manuscript.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/2162402X.2023.2238499

Additional information

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).