Cancer Immunology, Immunotherapy

, Volume 62, Issue 11, pp 1675–1685

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

  • 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
Original Article

DOI: 10.1007/s00262-013-1471-1

Cite this article as:
Pan, QZ., Pan, K., Zhao, JJ. et al. Cancer Immunol Immunother (2013) 62: 1675. doi:10.1007/s00262-013-1471-1

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.

Keywords

Hepatocellular carcinoma Interleukin-36α Prognosis Tumor-infiltrating lymphocytes 

Supplementary material

262_2013_1471_MOESM1_ESM.pdf (187 kb)
Supplementary material 1 (PDF 186 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Qiu-Zhong Pan
    • 1
  • Ke Pan
    • 1
  • Jing-Jing Zhao
    • 1
  • Ju-Gao Chen
    • 1
  • Jian-Jun Li
    • 1
  • Lin Lv
    • 1
  • Dan-Dan Wang
    • 1
  • Hai-Xia Zheng
    • 1
  • Shan-Shan Jiang
    • 1
  • Xiao-Fei Zhang
    • 1
  • Jian-Chuan Xia
    • 1
  1. 1.State Key Laboratory of Oncology in South China, Department of BiotherapySun Yat-Sen University Cancer CenterGuangzhouPeople’s Republic of China

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