Jebreel A, Mistry D, Loke D, Dunn G, Hough V, Oliver K, Stafford N, Greenman J
Department of Otolaryngology and Head and Neck Surgery, University of Hull, Hull, UK.
J Laryngol Otol. 2007 Mar;121(3):246-52. doi: 10.1017/S0022215106002428. Epub 2006 Aug 15.
Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial malignancy. It is the most common neoplasm arising in the upper aerodigestive tract. Interleukin (IL) 12 and IL-18 are cytokines which have a major anti-tumour activity via stimulation of a T-helper type 1 (Th1) immune response. Interleukin 10, a potent antagonist of IL-12, is a cytokine which possesses immunosuppressive activity mainly produced via T-helper type 2 (Th2) cells. Studies of other types of cancer have shown that the level of IL-12 in serum or tissues is suppressed and/or the IL-10 level is increased, suggesting that there is an impaired cell-mediated anti-tumour response. The aim of this study was to measure pre-operative serum cytokine concentrations in HNSCC patients in order to detect any changes in IL-10, IL-12 and IL-18, compared with non-tumour controls. The relationship between cytokine levels and standard clinicopathological features, including tumour site, tumour stage and presence of nodal metastasis, was also examined. Fifty-seven patients with primary HNSCC were prospectively recruited, together with 40 non-tumour control patients with a similar age and sex distribution. Serum cytokine levels were measured using commercial quantitative enzyme-linked immunosorbent assay. The HNSCC patients had significantly lower IL-12 levels (median; interquartile range) than controls (42.8 pg/ml, 26.2-61.6 vs 52.3 pg/ml, 37.5-113.7; p=0.018). Also, patients were more likely to have detectable IL-10 levels than were controls, as IL-10 was positive in 27/55 patients but in only 9/39 controls (p=0.011). Furthermore, IL-10 detectability varied according to primary site, being more commonly observed in hypopharyngeal and laryngeal tumours, and IL-10 was more likely to be detected with advanced tumour stage (T3 and T4). No differences in IL-18 levels were observed between patients and controls (p=0.169). These results suggest (in agreement with studies on other solid malignancies) that HNSCC causes a significant change in the serum levels of specific Th1 and Th2 cytokines, producing an in vivo environment that is unlikely to promote an effective cell-mediated anti-tumour response.
头颈部鳞状细胞癌(HNSCC)是一种侵袭性上皮恶性肿瘤。它是上呼吸道消化道最常见的肿瘤。白细胞介素(IL)-12和IL-18是通过刺激1型辅助性T细胞(Th1)免疫反应而具有主要抗肿瘤活性的细胞因子。白细胞介素10是IL-12的强效拮抗剂,是一种主要由2型辅助性T细胞(Th2)产生的具有免疫抑制活性的细胞因子。对其他类型癌症的研究表明,血清或组织中IL-12水平受到抑制和/或IL-10水平升高,这表明细胞介导的抗肿瘤反应受损。本研究的目的是测量HNSCC患者术前血清细胞因子浓度,以检测与非肿瘤对照组相比,IL-10、IL-12和IL-18的任何变化。还检查了细胞因子水平与标准临床病理特征之间的关系,包括肿瘤部位、肿瘤分期和淋巴结转移情况。前瞻性招募了57例原发性HNSCC患者以及40例年龄和性别分布相似的非肿瘤对照患者。使用商业定量酶联免疫吸附测定法测量血清细胞因子水平。HNSCC患者的IL-12水平(中位数;四分位间距)明显低于对照组(42.8 pg/ml,26.2 - 61.6 vs 52.3 pg/ml,37.5 - 113.7;p = 0.018)。此外,患者比对照组更有可能检测到IL-10水平,因为IL-10在55例患者中有27例呈阳性,而在39例对照中只有9例呈阳性(p = 0.011)。此外,IL-10的可检测性因原发部位而异,在下咽和喉肿瘤中更常见,并且随着肿瘤分期进展(T3和T4)更有可能检测到IL-10。患者与对照组之间未观察到IL-18水平的差异(p = 0.169)。这些结果表明(与其他实体恶性肿瘤的研究一致),HNSCC导致特定Th1和Th2细胞因子的血清水平发生显著变化,产生一种不太可能促进有效细胞介导抗肿瘤反应的体内环境。