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Abstract Details
Decreased expression of interleukin-36α correlates with poor prognosis in hepatocellular carcinoma
Pan QZ, Pan K, Zhao JJ, Chen JG, Li JJ, Lv L, Wang DD, Zheng HX, Jiang SS, Zhang XF, Xia JC. Cancer Immunol Immunother. 2013 Nov;62(11):1675-85. doi: 10.1007/s00262-013-1471-1. Epub 2013 Sep 6.
Source
State Key Laboratory of Oncology in South China, Department of Biotherapy, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.
Abstract
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.