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01.11.2013 | Original Article | Ausgabe 11/2013

Cancer Immunology, Immunotherapy 11/2013

Decreased expression of interleukin-36α correlates with poor prognosis in hepatocellular carcinoma

Cancer Immunology, Immunotherapy > Ausgabe 11/2013
Qiu-Zhong Pan, Ke Pan, Jing-Jing Zhao, Ju-Gao Chen, Jian-Jun Li, Lin Lv, Dan-Dan Wang, Hai-Xia Zheng, Shan-Shan Jiang, Xiao-Fei Zhang, Jian-Chuan Xia
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Electronic supplementary material

The online version of this article (doi:10.​1007/​s00262-013-1471-1) contains supplementary material, which is available to authorized users.
The authors Qiu-Zhong Pan and Ke Pan equally contributed to this work.


Interleukin-36α (IL-36α) has been found to have a prominent role in the pathogenesis of inflammatory disorders; however, little is known about the role of IL-36α in cancer. In this study, we investigated the expression, prognostic value, and the underlying antitumor mechanism of IL-36α in hepatocellular carcinoma (HCC). From immunohistochemistry analysis, IL-36α expression was lower in poorly differentiated HCC cells. In clinicopathological analysis, low IL-36α expression significantly correlated with tumor size, histological differentiation, tumor stage, and vascular invasion, and low intratumoral IL-36α expression had significantly worse overall survival rates and shorter disease-free survival rates. Moreover, intratumoral IL-36α expression was an independent risk factor for overall survival. Consecutive sections were used to detect CD3+, CD8+, and CD4+ tumor-infiltrating lymphocytes (TILs), and we found that high-IL-36α-expressing tumor tissues exhibited a significantly higher proportion of intratumoral CD3+ and CD8+ TILs, but not CD4+ TILs. Our in vitro model confirmed that supernatant from IL-36α-overexpressing human HCC cells had an increased capacity to recruit CD3+ and CD8+ T cells. Consistently, mouse HCC cells engineered to overexpress IL-36α demonstrated markedly delayed growth in vivo, as well as higher levels of intratumoral CD3+ and CD8+ TILs, compared with control mice. In vitro chemotaxis analysis also showed that mouse HCC cells overexpressing IL-36α could recruit more number of CD3+ and CD8+ T cells. These results show that IL-36α expression may play a pivotal role in determining the prognosis of patients with HCC, which we attribute to the activation of adaptive T cell immunity, especially CD8+ T cell immune response.

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