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

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.

SUBMITTER: Takada K

PROVIDER: S-EPMC5519175 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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

Takada Kazuki K Okamoto Tatsuro T Tominaga Masaki M Teraishi Koji K Akamine Takaki T Takamori Shinkichi S Katsura Masakazu M Toyokawa Gouji G Shoji Fumihiro F Okamoto Masaki M Oda Yoshinao Y Hoshino Tomoaki T Maehara Yoshihiko Y

PloS one 20170720 7

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 ...[more]

PMID: 28727766

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Project description:BACKGROUND:Vascular endothelial growth factor C (VEGFC), an activator of lymphangiogenesis, is newly identified as an immunomodulator which can regulate the immune system so that tumor cells more easily escape immune surveillance. Evidence has shown programmed cell death-ligand 1 (PD-L1) can also suppress the immune response. Nevertheless, the clinical significance of co-expression of VEGFC and PD-L1 for predicting outcomes in patients with lung adenocarcinoma has not yet been determined. METHODS:A total of 114 patients with lung adenocarcinoma who underwent surgeries at Tianjin Medical University Cancer Institute and Hospital between December 2011 and September 2016 were retrospectively reviewed. Tissue specimens were collected for immunohistochemistry of VEGFC and PD-L1 which were analyzed with an H-score system. RESULTS:In this study, 57 (50.0%) and 47 (41.2%) patients were classified as VEGFC high expression and PD-L1 high expression. Co-expression was observed in 33 (28.9%) patients. In addition, a positive correlation was found between VEGFC and PD-L1 (P = 0.0398, r = 0.1937). In a univariate analysis, both progression-free survival (PFS) and overall survival (OS) were significantly worse in the VEGFC high expression group and the PD-L1 high expression group, respectively. Furthermore, VEGFC/PD-L1 co-expression showed a worse OS (P = 0.03) and PFS survival (P = 0.01) than the other groups. CONCLUSIONS:Taken together, these results indicate that VEGFC/PD-L1 co-expression can forecast both poor OS and PFS in patients with resected lung adenocarcinoma. Co-expression of VEGFC and PD-L1 may serve as a significant prognostic factor for patients with lung adenocarcinoma. KEY POINTS:VEGFC/PD-L1 co-expression forecasts poor survival in patients with resected lung adenocarcinoma. VEGFC/PD-L1 co-expression may be used as a prognostic indicator and provide the theoretical possibility to screen the optimal population with a combination of anti-VEGFC and anti-PD-L1 therapy in the clinical treatment.

Dataset Information

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

Publications

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

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