Related Experiment Video

Updated: Dec 19, 2025

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
06:07

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors

Published on: August 5, 2022

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DNA hypomethylation promotes transposable element expression and activation of immune signaling in renal cell cancer

Aguirre A de Cubas1, William Dunker2, Andrew Zaninovich1

  • 1Division of Hematology and Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, and.

JCI Insight
|June 5, 2020
PubMed

Insights

Decitabine, a DNA hypomethylating agent, activates endogenous retroviruses (ERVs) and antiviral signaling, potentially improving immune checkpoint blockade response in kidney cancer. This strategy enhances T cell activity and migration, offering a new therapeutic avenue.

Area of Science:

  • Immunology
  • Oncology
  • Epigenetics

Background:

  • Endogenous retroviruses (ERVs) expression correlates with immune checkpoint blockade (ICB) response in renal cell carcinoma (RCC).
  • DNA hypomethylating agents may modulate the tumor immune microenvironment.

Purpose of the Study:

  • To investigate if decitabine, a DNA hypomethylating agent, can enhance ICB response by activating transposable element (TE) expression and antiviral signaling in kidney cancer.
  • To explore the mechanisms by which decitabine influences immune cell activity and migration.

Main Methods:

  • Decitabine treatment of kidney cancer cell lines and primary cells.
  • Knockout (KO) of RIG-I and MDA5 dsRNA sensors.
  • Immunoprecipitation (IP) assays.
  • Bioinformatic analyses of gene expression and immune infiltration.
  • Assessment of cytokine secretion and T cell activation/migration.
  • Retrospective analysis of metastatic clear cell RCC (ccRCC) patient data.

Main Results:

  • Decitabine activated transposable element (TE) expression (LINE1, ERVs) and antiviral signaling.
  • RIG-I and MDA5 were involved in decitabine-induced antiviral signaling and ERV binding.
  • Decitabine treatment promoted immune infiltration and was associated with ICB response.
  • Decitabine enhanced T cell activation and migration through cytokine secretion.
  • Responders to anti-PD1/PDL1 blockade showed higher activation of some antiviral genes.

Conclusions:

  • Decitabine induces transposable element (TE) expression and modulates innate antiviral pathways.
  • This epigenetic modulation enhances T cell action, suggesting a potential strategy to improve immune checkpoint blockade (ICB) efficacy in kidney cancer.
  • Targeting DNA methylation offers a novel approach to enhance anti-cancer immunotherapy.
Keywords:
Cellular immune responseImmunologyOncology

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