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Updated: Jun 2, 2025

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Increased SOAT2 expression in aged regulatory T cells is associated with altered cholesterol metabolism and reduced

Mingjiong Zhang1, Jiahua Cui2, Haoyan Chen1

  • 1Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Nature Communications
|January 13, 2025
PubMed

Insights

Sterol O-acyltransferase 2 (SOAT2) is overexpressed in aging regulatory T (Treg) cells, impairing anti-tumor immunity in lung cancer. Targeting SOAT2 may improve immunotherapy for elderly cancer patients.

Area of Science:

  • Immunology
  • Oncology
  • Aging Research

Background:

  • Immune functions decline with aging, increasing cancer susceptibility.
  • Identifying aging-related molecular targets in elderly cancer patients is crucial.
  • Regulatory T (Treg) cells play a key role in immune regulation and cancer progression.

Purpose of the Study:

  • To investigate the role of sterol O-acyltransferase 2 (SOAT2) in aging-related immune dysfunction in lung squamous cell carcinoma (LSCC).
  • To explore SOAT2 as a potential therapeutic target for enhancing anti-tumor immunity in elderly cancer patients.

Main Methods:

  • Analysis of SOAT2 expression in Treg cells from elderly LSCC patients.
  • Radiomics analysis of LSCC patient data.
  • Ex vivo human and mouse Treg cell experiments.
  • In vivo mouse tumor models.
  • Investigation of the SREBP2-HMGCR-GGPP pathway.

Main Results:

  • SOAT2 is overexpressed in Treg cells of elderly LSCC patients.
  • Increased SOAT2 expression correlates with reduced immune infiltration and poor prognosis in LSCC.
  • SOAT2 overexpression in Treg cells enhances cholesterol metabolism via the SREBP2-HMGCR-GGPP pathway.
  • SOAT2 promotes Treg suppressive functions while inhibiting CD8+ T cell proliferation, migration, and anti-tumor immunity.

Conclusions:

  • SOAT2 overexpression in Treg cells contributes to immune aging and impaired anti-tumor immunity.
  • SOAT2 represents a potential therapeutic target for improving immunotherapy outcomes in elderly cancer patients.

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