Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.
Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.
Surg Oncol. 2020 Mar;32:99-107. doi: 10.1016/j.suronc.2019.12.001. Epub 2019 Dec 7.
Growing evidences have demonstrated a pivotal role of chronic inflammation in oral squamous cell carcinoma (OSCC) through the modulation of inflammatory cells and cytokine production. IL-37 is newly discovered anti-inflammatory member of IL-1 family and can bind to IL-18 receptor to inhibit IL-18 (pro-inflammatory member of IL-1 family) function. Investigation on the balance of IL-18/IL-37 would provide new insights into the function of IL-1 family in OSCC. Thus, serum IL-18 and IL-37 levels of OSCC patients (n = 108), leukoplakia patients (n = 40), and healthy donors (n = 36) were collected to analyze the balance of IL-18 and IL-37, and also determine their diagnostic value and prognostic significance in OSCC. The results showed that OSCC patients had high IL-18 and low IL-37 levels in serum and peripheral blood mononuclear cell (PBMC). The ratio of IL-18/IL-37 in serum efficiently distinguished non-cancer individuals from OSCC patients (cut off value: 2.15). Moreover, patients with high IL-18 and low IL-37 were susceptible to develop advanced tumor stage and lymph node metastasis (Odd ratios of IL-18/IL-37 is 4.903 and 12.613, respectively). Meanwhile, higher IL-18/IL-37 ratio could predict shorter overall survival and disease-free survival of OSCC patients, although it was not an independent prognostic factor. We further analyze the correlations of serum IL-18/IL-37 with immunocytes in peripheral blood and found that high IL-18 level was associated with more CD19 B cells, while serum IL-37 seem to be associated with reduced percentage of CD3CD8 T cells, indicating its balance could change the adaptive immune response. Unexpectedly, we first revealed the different function of IL-18/IL-37 in serum and tumor tissues. High mRNA expression of IL-18 in tumor tissues correlated with low lymph node metastasis rate and low tumor stage, which was contradictory to the pro-tumor role of IL-18 in serum. In conclusion, enhanced ratio of IL-18/IL-37 level in serum could be an efficient biomarker for OSCC. Its balance might regulate CD19 B cells and CD3 CD8 T cells for OSCC progression.
越来越多的证据表明，慢性炎症通过调节炎症细胞和细胞因子的产生，在口腔鳞状细胞癌（OSCC）中起着关键作用。IL-37 是 IL-1 家族中新发现的抗炎成员，可与 IL-18 受体结合，抑制 IL-18（IL-1 家族中的促炎成员）的功能。研究 IL-18/IL-37 的平衡将为 IL-1 家族在 OSCC 中的功能提供新的见解。因此，收集了 108 例 OSCC 患者、40 例白斑病患者和 36 例健康供者的血清 IL-18 和 IL-37 水平，以分析 IL-18 和 IL-37 的平衡，并确定其在 OSCC 中的诊断价值和预后意义。结果表明，OSCC 患者血清和外周血单个核细胞（PBMC）中 IL-18 水平升高，IL-37 水平降低。血清中 IL-18/IL-37 比值能有效区分非癌症个体和 OSCC 患者（截断值：2.15）。此外，IL-18 水平高、IL-37 水平低的患者易发展为晚期肿瘤和淋巴结转移（IL-18/IL-37 的比值分别为 4.903 和 12.613）。同时，较高的 IL-18/IL-37 比值可预测 OSCC 患者的总生存期和无病生存期较短，尽管它不是独立的预后因素。我们进一步分析了血清 IL-18/IL-37 与外周血免疫细胞的相关性，发现高 IL-18 水平与更多的 CD19 B 细胞相关，而血清 IL-37 似乎与 CD3 CD8 T 细胞的百分比降低相关，表明其平衡可能改变适应性免疫反应。出乎意料的是，我们首次揭示了 IL-18/IL-37 在血清和肿瘤组织中的不同功能。肿瘤组织中 IL-18 的高 mRNA 表达与较低的淋巴结转移率和较低的肿瘤分期相关，这与 IL-18 在血清中的促肿瘤作用相反。总之，血清中 IL-18/IL-37 水平的比值升高可能是 OSCC 的有效生物标志物。其平衡可能调节 CD19 B 细胞和 CD3 CD8 T 细胞，促进 OSCC 的进展。
