IL-32 production from lung adenocarcinoma cells is potentially involved in immunosuppressive microenvironment

Med Mol Morphol. 2024 Jun;57(2):91-100. doi: 10.1007/s00795-023-00378-5. Epub 2024 Feb 6.

Abstract

Interleukin 32 (IL-32) is a proinflammatory cytokine secreted from several kinds of cancer cells. In the present study, we investigated the significance of IL-32 in lung adenocarcinoma by immunohistochemistry and bioinformatics analysis. IL-32 was positive in cancer cells of 21 cases (9.2%) of total 228 cases. Increased IL-32 gene expression was linked to worse clinical course in TCGA analysis, however, IL-32 expression in immunohistochemistry was not associated to clinical course in our cohort. It was also found that high IL-32 expression was seen in cases with increased lymphocyte infiltration. In vitro studies indicated that IFN-γ induced gene expression of IL-32 and PD1-ligands in lung adenocarcinoma cell lines. IL-32, especially IL-32β, also induced overexpression of PD1-ligands in human monocyte-derived macrophages. Additionally, Cancer-cell-derived IL-32 was elevated by stimulation with anticancer agents. In conclusion, IL-32 potentially induced by inflammatory conditions and anticancer therapy and contribute to immune escape of cancer cells via development the immunosuppressive microenvironment. IL-32 might be a target molecule for anti-cancer therapy.

Keywords: Adenocarcinoma; IL-32; Lung cancer; Macrophage; Tumor microenvironment.

MeSH terms

  • A549 Cells
  • Adenocarcinoma of Lung* / genetics
  • Adenocarcinoma of Lung* / immunology
  • Adenocarcinoma of Lung* / metabolism
  • Adenocarcinoma of Lung* / pathology
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukins* / genetics
  • Interleukins* / metabolism
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / immunology
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Tumor Microenvironment* / immunology

Substances

  • IL32 protein, human
  • Interleukins
  • Interferon-gamma