Clinical implications of the novel cytokine IL-38 expressed in lung adenocarcinoma: Possible association with PD-L1 expression

Kazuki Takada, Tatsuro Okamoto, Masaki Tominaga, Koji Teraishi, Takaki Akamine, Shinkichi Takamori, Masakazu Katsura, Gouji Toyokawa, Fumihiro Shoji, Masaki Okamoto, Yoshinao Oda, Tomoaki Hoshino, Yoshihiko Maehara

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Abstract

Interleukin (IL)-38, a novel member of the IL-1 cytokine family, is homologous to IL-1 receptor antagonist (IL-1Ra) and IL-36Ra, and has been reported to act as an antagonist. IL-38 expression is found in tonsil, placenta, and spleen, and recent studies suggest an association between IL-38 and autoimmune diseases. However, whether IL-38 plays a role in carcinogenesis or cancer growth is unclear. In the present study, we identified increases in IL-38 expression by immunohistochemistry in multiple types of cancer cells. In the examination of 417 surgically resected primary lung adenocarcinomas, Fisher’s exact tests showed significant associations between high IL-38 expression and high tumor grades, an advanced T status, advanced N status, advanced stage, and the presence of pleural and vessel invasions. Survival analyses by the Kaplan-Meier method showed that patients with high expression of IL-38 had significantly shorter disease-free survival and shorter overall survival after surgery than patients with low expression of IL-38 (log-rank test: P = 0.0021 and P = 0.0035, respectively). Moreover, programmed cell death-ligand 1 (PD-L1)-positive cases showed higher expression of IL-38 than PD-L1-negative cases (Wilcoxon rank-sum test: P < 0.0001). In conclusion, IL-38 was expressed in tumor cells of various cancers, and IL-38 expression was associated with poor survival of lung adenocarcinoma patients. IL-38 may affect host immunity or the tumor microenvironment, and contribute to the progression of lung adenocarcinoma.

Original languageEnglish
Article numbere0181598
JournalPloS one
Volume12
Issue number7
DOIs
Publication statusPublished - Jul 2017

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Interleukins
Cell death
interleukins
adenocarcinoma
Cell Death
cytokines
apoptosis
lungs
Cytokines
Ligands
Tumors
neoplasms
interleukin-1
Neoplasms
Nonparametric Statistics
ligands
Adenocarcinoma of lung
antagonists
Cells
Tumor Microenvironment

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Takada, K., Okamoto, T., Tominaga, M., Teraishi, K., Akamine, T., Takamori, S., ... Maehara, Y. (2017). Clinical implications of the novel cytokine IL-38 expressed in lung adenocarcinoma: Possible association with PD-L1 expression. PloS one, 12(7), [e0181598]. https://doi.org/10.1371/journal.pone.0181598

Clinical implications of the novel cytokine IL-38 expressed in lung adenocarcinoma : Possible association with PD-L1 expression. / Takada, Kazuki; Okamoto, Tatsuro; Tominaga, Masaki; Teraishi, Koji; Akamine, Takaki; Takamori, Shinkichi; Katsura, Masakazu; Toyokawa, Gouji; Shoji, Fumihiro; Okamoto, Masaki; Oda, Yoshinao; Hoshino, Tomoaki; Maehara, Yoshihiko.

In: PloS one, Vol. 12, No. 7, e0181598, 07.2017.

Research output: Contribution to journalArticle

Takada, K, Okamoto, T, Tominaga, M, Teraishi, K, Akamine, T, Takamori, S, Katsura, M, Toyokawa, G, Shoji, F, Okamoto, M, Oda, Y, Hoshino, T & Maehara, Y 2017, 'Clinical implications of the novel cytokine IL-38 expressed in lung adenocarcinoma: Possible association with PD-L1 expression', PloS one, vol. 12, no. 7, e0181598. https://doi.org/10.1371/journal.pone.0181598
Takada, Kazuki ; Okamoto, Tatsuro ; Tominaga, Masaki ; Teraishi, Koji ; Akamine, Takaki ; Takamori, Shinkichi ; Katsura, Masakazu ; Toyokawa, Gouji ; Shoji, Fumihiro ; Okamoto, Masaki ; Oda, Yoshinao ; Hoshino, Tomoaki ; Maehara, Yoshihiko. / Clinical implications of the novel cytokine IL-38 expressed in lung adenocarcinoma : Possible association with PD-L1 expression. In: PloS one. 2017 ; Vol. 12, No. 7.
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