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Interleukin-36α inhibits colorectal cancer metastasis by enhancing the infiltration and activity of CD8+ T lymphocytes
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  • Yahong Wu,
  • xiuyu wei,
  • yongjie yao,
  • xiaoxi wang,
  • jiaxin sun,
  • lu qiu,
  • yuanming qi,
  • yanfeng gao,
  • Wenjie Zhai,
  • Wenshan Zhao
Yahong Wu
Zhengzhou University

Corresponding Author:[email protected]

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xiuyu wei
Zhengzhou University
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yongjie yao
Zhongshan University
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xiaoxi wang
Zhengzhou University
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jiaxin sun
Zhengzhou University
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lu qiu
Zhengzhou University
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yuanming qi
Zhengzhou University
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yanfeng gao
Zhengzhou University
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Wenjie Zhai
Zhengzhou University
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Wenshan Zhao
Zhengzhou University
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Abstract

Colorectal cancer is one of the deadliest cancers, and the discovery of new diagnostic biomarkers and therapeutic targets is vital. Interleukin-36α (IL-36α) is a proinflammatory factor that can initiate the inflammatory response and promote the systemic T helper-1 (Th1) immune response. In this study, we investigated the immunological role of IL-36α in CRC. We found that IL-36α was downregulated in human CRC tissues. Patients with high IL-36α levels showed better survival and low IL-36α expression was significantly associated with greater tumor distal metastasis and TNM stage. We constructed two cell lines overexpressing IL-36α (CT26-IL-36α and HT29-IL-36α cells). In vitro assays revealed that IL-36α overexpression reduced the proliferation, migration, and invasion of CT26-IL-36α, and HT29-IL-36α cells. Using CT26-vector and CT26-IL-36α tumor xenograft and lung metastasis models, we found that IL-36α overexpression elicited a significant antitumor effect and inhibited lung metastasis in vivo. These inhibitory effects were associated with an increase in the number of CD3+CD8+ T lymphocytes within the tumor tissue as well as increased cytokine production in CD8+ T lymphocytes present in the tumor, spleen, and draining lymph nodes. Furthermore, we revealed that CT26-IL-36α cells enhanced the secretion of CXCL10 and CXCL11 from chemotactic CD8+ T lymphocytes, as compared with CT26-vector cells. Taken together, these results suggest that IL-36α is a promising therapeutic agent for targeting CRC by promoting the activation, proliferation, and tumor infiltration of T lymphocytes.