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Deficiency of IL-18 Aggravates Esophageal Carcinoma Through Inhibiting IFN-γ Production by CD8+T Cells and NK Cells

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Abstract

To investigate the potential role of interleukin-18 (IL-18) in immunomodulation during tumorigenesis of esophageal carcinoma and elucidate the underlying molecular mechanism, we employed IL-18 knockout mice for this purpose. Carcinogen 4-nitroquinoline 1-oxide (4NQO) was administrated in drinking water to induce occurrence of esophageal squamous cell carcinoma (ESCC). T cell activation as indicated by the surface CD molecules was analyzed with flow cytometry. The serous content of interferon-γ (IFN-γ) along with other cytokines was determined by inflammatory human cytokine cytometric bead array. The cytotoxicity assay was performed by co-culture of tumor cells with immune cells and relative cell viability was determined by lactate dehydrogenase (LDH) assay. Apoptotic cells were stained with Annexin-V/propidium iodide (PI) and analyzed by flow cytometry. Cell proliferation was measured with Cell Counting Kit-8 (CCK-8) assay. Our data demonstrated that deficiency of IL-18 promoted the progression and development of 4NQO-induced ESCC. Loss of IL-18 suppressed the activation of T cells in the esophagus. Deficiency of IL-18 inhibited the IFN-γ production by CD8+ T cells and natural killer (NK) cells. Absence of IL-18 inhibited the cytotoxicity of CD8+ T cells and NK cell in vitro. Moreover, deficiency of IL-18 promoted the apoptosis of CD8+ T cells and inhibited the proliferation of CD8+ T cells in vitro. Our data elucidated the immunomodulatory role of IL-18 during tumorigenesis of ESCC, whose deficiency compromised antitumor immunity and contributed to immune escape of esophageal carcinoma. Our results also indicated the therapeutic potential of exogenous IL-18 against ESCC, which warrants further investigations.

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Authors and Affiliations

  1. Hebei Medical University, No. 361 East Zhongshan Road, Shijiazhuang, Hebei, 050017, China

    Jiantao Li, Xiaohui Dai & Jianhui Cai

  2. Hebei General Hospital, No. 348 West Heping Road, Shijiazhuang, Hebei, 050051, China

    Jiantao Li, Gang Qiu & Baoshuan Fang

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  1. Jiantao Li
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  2. Gang Qiu
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Correspondence to Jianhui Cai.

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Li, J., Qiu, G., Fang, B. et al. Deficiency of IL-18 Aggravates Esophageal Carcinoma Through Inhibiting IFN-γ Production by CD8+T Cells and NK Cells. Inflammation 41, 667–676 (2018). https://doi.org/10.1007/s10753-017-0721-3

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