Investigation of Th1/Th2 cytokine profiles in patients with laryngo-pharyngeal, HPV-positive cancers
Investigation of Th1/Th2 cytokine profiles in patients with laryngo-pharyngeal, HPV-positive cancers
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DOI：
10.1007/s00405-012-2067-7
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发表时间：
2013-02-01
影响因子：
2.6
通讯作者：
Cernescu, Costin
中科院分区：
文献类型：
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作者：
Bleotu, Coralia;Chifiriuc, Mariana Carmen;Cernescu, Costin
本研究的目的是揭示喉咽癌患者原发肿瘤的特征、肿瘤分期程度、血液中人乳头瘤病毒（HPV）的存在与Th1/Th2血清细胞因子失衡的严重程度之间的关系。研究纳入50例患者（男性47例，女性3例），年龄40 ~ 83岁（平均年龄58.4±9.43岁，中位60岁）。对照组为年龄匹配的健康患者（无临床疾病）。采用PCR检测病毒DNA；ELISA法检测细胞因子水平。在癌症患者中，细胞因子Th1明显转换为细胞因子Th2，晚期患者IL-2和IFN γ水平较低，IL-2和IL-12水平升高与早期喉咽癌呈正相关。局部区域转移与IL-8和IL-10水平升高以及IFN γ急剧下降相关。在癌症晚期，我们发现受影响最大的是与Th2细胞因子水平升高相关的IL-2和IFN γ。原发肿瘤和血液中同时存在HPV的患者与仅存在HPV阳性的原发肿瘤患者相比，IL-4:IL-2比值升高，表明免疫抑制状态加重。本研究最重要的发现是，为了正确评估癌症患者的Th1到Th2转换，不仅需要建立不同Th1和Th2型细胞因子之间的负/正相关关系，还需要建立它们之间的比值。这些参数使我们能够说明，血液中HPV DNA的存在与最严重的免疫失衡有关，这可能导致这些患者预后不良。我们的研究结果鼓励我们考虑不同Th1和Th2细胞因子之间的比例可以代表癌症患者临床和病理评估的有用标记。
The aim of this study was to reveal the relationships between the features of the primary tumour, the degree of tumour stage, the presence of human papillomaviruses (HPV) in blood and the severity of Th1/Th2 serum cytokine imbalance in patients with laryngo-pharyngeal cancer. The study was performed on 50 patients (47 men and 3 women), with age ranging from 40 to 83 years (the mean of the patients' ages was 58.4 +/- A 9.43 years, with a median of 60 years). A control group was represented by age-matched healthy patients (with no clinical diseases). The viral DNA was detected by PCR; the cytokine levels were determined by ELISA. A clear switch from cytokine Th1 to cytokine Th2 in cancer patients, low levels of IL-2 and IFN gamma in advanced stages, as well as a positive correlation of increased levels of both IL-2 and IL-12 with the early stages of laryngo-pharyngeal cancer was observed. Loco-regional metastases were correlated with increased levels of IL-8 and IL-10 and drastic decrease of IFN gamma. In advanced cancer stages, we found that the most affected were IL-2 and IFN gamma correlated with increased levels of Th2 cytokines. Patients with HPV present in both primary tumours and blood showed increased values of IL-4:IL-2 ratio as compared with patients with HPV-positive primary tumours only, demonstrating the aggravation of the immunosuppressive state. The most important finding of our study is that for a correct evaluation of the Th1 to Th2 switch in cancer patients, it is necessary to establish not only the negative/positive correlations between different Th1 and Th2 type cytokines, but also the ratio between them. These parameters allowed us to state that the presence of HPV DNA in blood was associated with the most severe immunological imbalance that could potentially lead to a poor prognosis of these patients. Our findings encourage us to consider that the ratio between different Th1 and Th2 cytokines could represent a useful marker for clinical and pathological evaluation of cancer patients.