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

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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.

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The data presented in this study are available in this article and its supplementary materials.

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Acknowledgements

We thank Ms. Yuka Watanabe for the technical assistance. Lianbo Li was supported by the Otsuka Toshimi Scholarship Foundation, enabling the successful completion of this project.

Funding

This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Nos. 20H03459).

Author information

Authors and Affiliations

  1. Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1, Honjo, Kumamoto Chuo-ku, Kumamoto, 860-8556, Japan

    Shukang Zhao, Lianbo Li, Yoshihiro Komohara, Eri Matsubara, Ahmad Adawy, Hiromu Yano, Cheng Pan & Yukio Fujiwara

  2. Department of Thoracic Surgery and Breast Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

    Shukang Zhao, Eri Matsubara, Yusuke Shinchi, Koei Ikeda & Makoto Suzuki

  3. Department of Pediatric Surgery and Transplantation, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

    Lianbo Li, Ahmad Adawy & Taizo Hibi

  4. Center for Metabolic Regulation of Healthy Aging, Kumamoto University, Kumamoto, Japan

    Yoshihiro Komohara

  5. Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan

    Shinya Suzu

Authors
  1. Shukang Zhao
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  2. Lianbo Li
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  3. Yoshihiro Komohara
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  7. Hiromu Yano
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  8. Cheng Pan
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  13. Makoto Suzuki
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Corresponding author

Correspondence to Yoshihiro Komohara.

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Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

The study was approved by the Institutional Review Board of Kumamoto University (#1174), and conducted in accordance with the Declaration of Helsinki. Human macrophages were obtained from healthy donors in accordance with protocols approved by the Kumamoto University Hospital Review Board (approval No. 1169. No animal studies or registry/registration of this study was performed.

Consent to participate

Patient consent for inclusion in this study was waived by the Institutional Review Board of Kumamoto University (#2059) because the OS and PFS data were obtained from previous reports [7]. Although all of the retrospective patient data were automatically included in the study, the patients were given the opportunity to refuse participation by opting out.

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Informed consent for publication was obtained from the relevant participants.

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Zhao, S., Li, L., Komohara, Y. et al. IL-32 production from lung adenocarcinoma cells is potentially involved in immunosuppressive microenvironment. Med Mol Morphol 57, 91–100 (2024). https://doi.org/10.1007/s00795-023-00378-5

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  • DOI: https://doi.org/10.1007/s00795-023-00378-5

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