Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Kumamoto Chuo-ku, Kumamoto, 860-8556, Japan.
Department of Thoracic Surgery and Breast Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Med Mol Morphol. 2024 Jun;57(2):91-100. doi: 10.1007/s00795-023-00378-5. Epub 2024 Feb 6.
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.
白细胞介素 32（IL-32）是一种由多种癌细胞分泌的促炎细胞因子。本研究通过免疫组织化学和生物信息学分析，探讨了 IL-32 在肺腺癌中的意义。在总共 228 例病例中，21 例（9.2%）的癌细胞呈 IL-32 阳性。TCGA 分析表明，IL-32 基因表达增加与更差的临床病程相关，但我们的队列中 IL-32 表达与临床病程无关。还发现，高 IL-32 表达与淋巴细胞浸润增加的病例相关。体外研究表明，IFN-γ 诱导肺腺癌细胞系中 IL-32 和 PD1 配体的基因表达。IL-32，特别是 IL-32β，也诱导人单核细胞衍生巨噬细胞中 PD1 配体的过表达。此外，抗癌药物刺激可使癌细胞来源的 IL-32 升高。总之，IL-32 可能由炎症条件和抗癌治疗诱导，并通过发展免疫抑制微环境促进癌细胞的免疫逃逸。IL-32 可能是抗癌治疗的靶分子。
