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Updated: Nov 17, 2025

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
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Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

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USP22 deficiency in melanoma mediates resistance to T cells through IFNγ-JAK1-STAT1 signal axis

Min Li1, Yanqin Xu1, Jie Liang2

  • 1Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, People's Republic of China; Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University, Shanghai, People's Republic of China.

Molecular Therapy : the Journal of the American Society of Gene Therapy
|February 18, 2021
PubMed

Insights

Ubiquitin specific peptidase 22 (USP22) loss impairs melanoma's ability to evade T-cell attacks. USP22 deubiquitinates STAT1, enhancing its stability and boosting anti-tumor immunity during immunotherapy.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Genome-wide CRISPR-Cas9 screens identify genes influencing phenotypes.
  • Understanding tumor escape mechanisms is crucial for effective cancer immunotherapy.

Purpose of the Study:

  • To identify genes involved in melanoma's evasion of T-cell-mediated killing.
  • To investigate the role of ubiquitin specific peptidase 22 (USP22) in anti-tumor immunity.

Main Methods:

  • Utilized genome-wide CRISPR-Cas9 loss-of-function screens in melanoma cells.
  • Assessed the impact of USP22 deletion and overexpression on T-cell-mediated killing in vitro and in vivo.
  • Analyzed USP22's interaction with STAT1 and its effect on the interferon pathway in melanoma cells.

Main Results:

  • Interferon gamma (IFNγ) signaling genes were enriched in T-cell-resistant melanoma.
  • USP22 deletion decreased T-cell killing efficacy, while overexpression increased sensitivity.
  • USP22 deficiency impaired interferon pathway sensitivity and correlated with its key molecules in clinical samples.
  • USP22 was found to deubiquitinate and stabilize STAT1.

Conclusions:

  • USP22 plays a critical role in melanoma's escape from CD8+ T-cell effector functions.
  • USP22's interaction with STAT1 is a key mechanism influencing anti-tumor immunity.
  • Targeting USP22 may represent a novel therapeutic strategy to enhance immunotherapy efficacy in melanoma.
Keywords:
STAT1USP22deubiquitinationimmunotherapy

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