Activation of cGAS-STING Signal to Inhibit the Proliferation of Bladder Cancer: The Immune Effect of Cisplatin

Cells. 2022 Sep 27;11(19):3011. doi: 10.3390/cells11193011.

Abstract

Cisplatin is commonly used in neoadjuvant, adjuvant, and systemic therapy for advanced bladder cancer, but its immune-related mechanism is still unclear. Exploration of the immune effects of cisplatin in bladder cancer would complement the comprehensive mechanism of cisplatin and provide the basis for combination therapy of cisplatin and immunotherapy in bladder cancer. We confirmed the immune effects of cisplatin on T24 and TCCSUP bladder cancer cell lines in vitro and explored the important function of these immune effects in the bladder cancer microenvironment in a mice tumor model. We found cisplatin induced immune response in bladder cancer by RNA sequencing and validated that cGAS-STING signal was deeply involved in this response. Cisplatin induced cGAS-STING signal inhibited the proliferation of bladder cancer and increased the infiltration percentages of CD8+ T cells and dendritic cells in a transplantation mice tumor model. Accumulation of dsDNA and the release of chromatin bound cGAS are important to activate downstream STING. Our findings indicated a cisplatin-related immune effect in bladder cancer, and cisplatin combined with immunotherapy might have a synergistic effect for bladder cancer therapy.

Keywords: DNA damage; bladder cancer; cGAS-STING; chromatin bound; cisplatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Chromatin
  • Cisplatin* / pharmacology
  • Cisplatin* / therapeutic use
  • Membrane Proteins / metabolism*
  • Mice
  • Nucleotidyltransferases / metabolism
  • Tumor Microenvironment
  • Urinary Bladder Neoplasms* / drug therapy

Substances

  • Chromatin
  • Membrane Proteins
  • Sting1 protein, mouse
  • Nucleotidyltransferases
  • Cisplatin

Grants and funding

This work was supported by the Key Project of Science and Technology Program of Zhejiang Province (grant no. 2020C03026) and Zhejiang Provincial Natural Science Foundation of China (grant no. LQ21H160019).