CHST4 associates with high-abundance immune infiltration in hormone receptor-positive breast cancer

J Leukoc Biol. 2024 Dec 31;117(1):qiae190. doi: 10.1093/jleuko/qiae190.

Abstract

Hormone receptor-positive breast cancer (HR+ BRCA) with high-risk factors such as lymph node metastasis has a relatively poor prognosis. However, the biological basis of tumor cell migration is still poorly understood, especially as some of the metastatic events occur at an early stage. Here, we identified that CHST4 (carbohydrate sulfotransferase 4), which has an important role in lymphocyte homing, was abnormally downregulated in HR+ BRCA and associated with lymph node metastasis. By enrichment analysis and immune infiltration evaluation, we predicted the potential ability of CHST4 to enhance immune cell infiltration. Then, immunohistochemical staining further demonstrated the contribution of CHST4 to the infiltration abundance of CD8+ T cells and CD4+ T cells in HR+ BRCA. Immunohistochemical staining of MECA-79 further identified the correlation between CHST4 and sulfated peripheral node addressin. Finally, we demonstrated that CHST4 was connected to increased tumor-immune cell communication by analyzing single-cell sequencing data. In summary, our study provided novel insights into the regulation of HR+ BRCA immune infiltration by CHST4.

Keywords: CHST4; hormone receptor-positive breast cancer; immune cell infiltration; metastasis.

MeSH terms

  • Breast Neoplasms* / immunology
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphatic Metastasis
  • Lymphocytes, Tumor-Infiltrating* / immunology
  • Lymphocytes, Tumor-Infiltrating* / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Sulfotransferases* / genetics
  • Sulfotransferases* / metabolism

Substances

  • Sulfotransferases
  • Receptors, Estrogen
  • Receptors, Progesterone