Related Experiment Video

Updated: Jul 12, 2026

Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports
07:44

Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports

Published on: November 28, 2019

A micropeptide encoded by the lncRNA USP30-AS1 promotes tumor growth by attenuating cGAS-STING-type I IFN signaling

Xingwen Wang1,2,3,4, Yi Zhang1,2, Jiangwen Ma1,2

  • 1School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.

Nature Cancer
|July 9, 2026
PubMed

Insights

Researchers discovered a micropeptide, UEIS, that suppresses anti-tumor immunity by reprogramming macrophages. Inhibiting UEIS enhances T cell responses and improves cancer treatment efficacy, offering a new therapeutic target.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cancer Research

Background:

  • Immune checkpoint blockade (ICB) shows promise in cancer therapy, but efficacy enhancement is crucial.
  • Tumor-associated macrophages (TAMs) play a complex role in the tumor microenvironment, often suppressing anti-tumor immunity.

Purpose of the Study:

  • To identify and characterize novel immunoregulatory factors within tumor-associated macrophages.
  • To elucidate the mechanism by which these factors influence anti-tumor T cell responses.
  • To explore potential therapeutic targets for enhancing ICB efficacy.

Main Methods:

  • Identification of a micropeptide encoded by USP30-AS1 long noncoding RNA.
  • Investigation of the micropeptide's role in macrophage polarization and function.
  • Analysis of the cGAS-STING-type I interferon signaling pathway.
  • Biochemical assays to study protein-protein interactions and condensate formation.
  • In vivo studies using peptide inhibitors in tumor models.

Main Results:

  • A novel micropeptide, UEIS (USP30-AS1-encoded immune suppressor), was identified in TAMs.
  • UEIS promotes a protumorigenic macrophage phenotype, suppressing T cell immunity.
  • UEIS is induced by cGAS-STING-type I interferon signaling and negatively regulates it by inhibiting TBK1-STING interaction via biomolecular condensate formation.
  • Disruption of UEIS-TBK1 condensation with a peptide inhibitor reduced tumor growth and enhanced ICB response.

Conclusions:

  • UEIS is a key mediator of immunosuppression in the tumor microenvironment.
  • Targeting UEIS-TBK1 interactions presents a promising strategy to overcome resistance to immune checkpoint blockade.
  • UEIS represents a novel therapeutic target for enhancing cancer immunotherapy.

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