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Suppression of protein quality control system by TRIM30a sensitises tumour cells to NK cell-mediated immune

Lukman O Afolabi1,2, Jiacheng Bi1,2,3, Liang Chen2,4

  • 1Guangdong Immune Cell Therapy Engineering and Technology Research Center, Center for Protein and Cell-based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.

Immunology
|September 27, 2023
PubMed

Insights

Overexpression of tripartite motif-containing protein 30a (TRIM30a) impairs tumor cell protein quality control, making them vulnerable to natural killer (NK) cell attacks. This suggests TRIM30a acts as a tumor suppressor by enhancing immune surveillance.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cancer Research

Background:

  • Tumorigenesis involves evading cellular regulation and host defenses.
  • The role of protein quality control (PQC) in tumor immune evasion is not fully understood.

Purpose of the Study:

  • To investigate the impact of tripartite motif-containing protein 30a (TRIM30a) on tumor cell susceptibility to immune surveillance.
  • To elucidate the mechanisms by which TRIM30a influences tumor growth and immune evasion.

Main Methods:

  • Overexpression of TRIM30a in tumor cells.
  • In vitro proliferation and apoptosis assays.
  • In vivo tumor growth studies in immune-competent and NK cell-depleted mice.
  • Analysis of protein quality control pathways, reactive oxygen species production, and gene expression.

Main Results:

  • TRIM30a overexpression sensitized tumor cells to natural killer (NK) cell-mediated killing without affecting proliferation or apoptosis in vitro.
  • TRIM30a-overexpressing tumors grew slower in immune-competent mice but not in NK cell-depleted mice.
  • TRIM30a impaired protein clearance, increased reactive oxygen species, and reduced proteasome and antioxidant gene expression, indicating compromised PQC.

Conclusions:

  • TRIM30a acts as a tumor suppressor and immune modulator by enhancing NK cell-mediated tumor cell lysis.
  • Impaired protein quality control and antioxidant capacity are integral to tumor immune escape mechanisms.
Keywords:
antioxidant response elementcytotoxicitynatural killer cellproteasomeprotein quality controltripartite motif-containing protein 30a

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