Interleukin-37 Mediates the Antitumor Activity in Hepatocellular Carcinoma: Role for CD57+ NK Cells

• Published in: Scientific reports Vol. 4; no. 1; p. 5177
• Main Authors: Zhao, Jing-Jing, Pan, Qiu-Zhong, Pan, Ke, Weng, De-Sheng, Wang, Qi-Jing, Li, Jian-Jun, Lv, Lin, Wang, Dan-Dan, Zheng, Hai-Xia, Jiang, Shan-Shan, Zhang, Xiao-Fei, Xia, Jian-Chuan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05-06-2014; Nature Publishing Group
• Subjects: 13; 13/51; 631/250/127/1213; 631/67/327; Animals; Antitumor activity; Apoptosis; Carcinoma, Hepatocellular - immunology; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - mortality; Carcinoma, Hepatocellular - prevention & control; CD3 antigen; CD57 antigen; CD57 Antigens - metabolism; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - pathology; Cell Proliferation; Chemotaxis; Cytokines; Female; Hepatocellular carcinoma; Humanities and Social Sciences; Humans; Immunoenzyme Techniques; Interleukin-1 - metabolism; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Killer Cells, Natural - pathology; Liver cancer; Liver Neoplasms - immunology; Liver Neoplasms - metabolism; Liver Neoplasms - mortality; Liver Neoplasms - prevention & control; Lymphocytes T; Male; Medical prognosis; Mice; Mice, Inbred C57BL; Middle Aged; multidisciplinary; Natural killer cells; Prognosis; Science; Survival; Survival Rate; Tumor Cells, Cultured; Tumors; Xenograft Model Antitumor Assays
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep05177

The biological role of interleukin-37 (IL-37) in cancer is large unknown. Through immunohistochemical detection using 163 primary hepatocellular carcinoma (HCC) clinical specimens, we found the expression of IL-37 was decreased in tumor tissues and the expression level was negatively correlated with tumor size. High expression of IL-37 in HCC tumor tissues was associated with better overall survival (OS) and disease-free survival (DFS). IL-37 expression in tumor tissues was positively associated with the density of tumor-infiltrating CD57+ natural killer (NK) cells, but not with the CD3+ and CD8+ T cells. Consistently,
in vitro
chemotaxis analysis showed that IL-37- overexpressing HCC cells could recruit more NK cells. The
in vivo
mouse model experiments also revealed that overexpression IL-37 in HCC cells significantly delayed tumor growth and recruited more NK cells into tumors tissues. Our finding suggested that IL-37 might play an important role for the prognosis of HCC patients via regulating innate immune-action.