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Emerging roles of USP7 in tumor immune evasion, metabolic reprogramming, and therapeutic resistance

Xiaolin Liu1, Bo Chi Zhu2, Li Li Lian2

  • 1Norman Bethune Second Clinical Medical College, Jilin University, Changchun, Jilin, China.

Frontiers in Immunology
|June 5, 2026
PubMed

Insights

Ubiquitin-specific protease 7 (USP7) regulates cancer progression by impacting immune evasion and metabolism. Inhibiting USP7 shows promise for overcoming therapeutic resistance and improving cancer treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Ubiquitin-specific protease 7 (USP7) is a deubiquitinase crucial for cancer progression.
  • USP7 influences tumor immune evasion, metabolic adaptation, and therapeutic resistance.

Purpose of the Study:

  • To review the multifaceted roles of USP7 in cancer immunity and metabolism.
  • To discuss the therapeutic potential and challenges of targeting USP7 in cancer treatment.

Main Methods:

  • Literature review of USP7 structure, substrate networks, and functions.
  • Analysis of USP7's involvement in immune suppression and metabolic adaptation.
  • Evaluation of USP7 inhibition strategies in preclinical and clinical settings.

Main Results:

  • USP7 stabilizes immune checkpoint molecules (e.g., PD-L1) and modulates immune signaling, promoting immune suppression.
  • USP7 maintains metabolic homeostasis, including lipid balance, redox status, and ferroptosis resistance, supporting tumor survival.
  • USP7 contributes to resistance against various anticancer therapies, including immune checkpoint blockade.

Conclusions:

  • USP7 plays a critical role in coordinating tumor immunity and metabolism, driving cancer progression and therapeutic resistance.
  • Targeting USP7 offers a promising strategy for reprogramming the tumor microenvironment and enhancing combination therapies.
  • Further research is needed to address translational challenges for effective USP7-targeted cancer therapies.
Keywords:
USP7metabolic reprogrammingtherapeutic resistancetumor immune evasiontumor microenvironment

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