Reshaping tumor microenvironment by regulating local cytokines expression with a portable smart blue-light controlled device

Commun Biol. 2024 Jul 29;7(1):916. doi: 10.1038/s42003-024-06566-y.

Abstract

Cytokines have attracted sustained attention due to their multi-functional cellular response in immunotherapy. However, their application was limited to their short half-time, narrow therapeutic window, and undesired side effects. To address this issue, we developed a portable smart blue-light controlled (PSLC) device based on optogenetic technology. By combining this PSLC device with blue-light controlled gene modules, we successfully achieved the targeted regulation of cytokine expression within the tumor microenvironment. To alter the tumor microenvironment of solid tumors, pro-inflammatory cytokines were selected as blue-light controlled molecules. The results show that blue-light effectively regulates the expression of pro-inflammatory cytokines both in vitro and in vivo. This strategy leads to enhanced and activated tumor-infiltrating immune cells, which facilitated to overcome the immunosuppressive microenvironment, resulting in significant tumor shrinkage in tumor-bearing mice. Hence, our study offers a unique strategy for cytokine therapy and a convenient device for animal studies in optogenetic immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cytokines* / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunotherapy / methods
  • Light*
  • Mice
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / therapy
  • Optogenetics* / instrumentation
  • Optogenetics* / methods
  • Tumor Microenvironment*

Substances

  • Cytokines