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食管癌或食管胃交界腺癌患者的淋巴细胞亚群及T(h)1/T(h)2免疫反应:与pTNM分期及临床结局的关系

Lymphocyte subsets and T(h)1/T(h)2 immune responses in patients with adenocarcinoma of the oesophagus or oesophagogastric junction: relation to pTNM stage and clinical outcome.

作者信息

van Sandick Johanna W, Boermeester Marja A, Gisbertz Suzanne S, ten Berge Ineke J M, Out Theo A, van der Pouw Kraan Tineke C T M, van Lanschot J Jan B

机构信息

Department of Surgery, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

出版信息

Cancer Immunol Immunother. 2003 Oct;52(10):617-24. doi: 10.1007/s00262-003-0406-7. Epub 2003 Jun 12.

Abstract

INTRODUCTION

Recent studies have indicated that the cytokines produced by CD4(+) T helper type 1 (T(h)1) and type 2 (T(h)2) cells are critically important in antitumour immunity and perhaps clinical outcome. From this perspective, we investigated the immunocompetence of patients with previously untreated cancer of the oesophagus or oesophagogastric junction (OGJ) in relation to stage of disease and postoperative survival.

METHODS

Blood samples were taken prior to surgery from 32 patients with adenocarcinoma of the oesophagus or OGJ. Ten healthy volunteers served as normal controls. T-cell and monocyte subpopulations were determined using flow cytometry. Monocyte as well as T(h)1- and T(h)2-lymphocyte cytokine levels were assessed in stimulated whole blood cultures.

RESULTS

Absolute T-cell and monocyte (subset) counts as well as monocyte cytokine levels were similar among patients and controls. Production of T(h)1-type cytokines was higher in patients than in controls (IFN-gamma, p=0.01; IL-2, p=0.05), whereas T(h)2-type cytokine levels were comparable (IL-4, p=0.5; IL-13, p=0.3). T-cell CD4(+)/CD8(+) ratios decreased as pTNM stage worsened (stage I/II vs stage III/IV, p=0.009). Of all measured immunological parameters, only IL-2 production significantly affected both overall survival ( p=0.015) and disease-free survival ( p=0.0062). High IL-2 levels corresponded with a favourable prognosis.

CONCLUSIONS

Patients awaiting surgery for adenocarcinoma of the oesophagus or oesophagogastric junction demonstrated a shift in the T(h)1/T(h)2 balance-in favour of T(h)1-compared with healthy volunteers. The ability of T cells to produce IL-2 was related to survival indicating a crucial role of T(h)1-type cells in antitumour immunosurveillance.

摘要

引言

近期研究表明,CD4(+) 1型辅助性T细胞(T(h)1)和2型辅助性T细胞(T(h)2)产生的细胞因子在抗肿瘤免疫乃至临床结局中起着至关重要的作用。从这一角度出发,我们研究了未经治疗的食管癌或食管胃交界(OGJ)癌患者的免疫能力与疾病分期及术后生存率的关系。

方法

对32例食管或OGJ腺癌患者在手术前采集血样。10名健康志愿者作为正常对照。使用流式细胞术测定T细胞和单核细胞亚群。在刺激的全血培养物中评估单核细胞以及T(h)1和T(h)2淋巴细胞的细胞因子水平。

结果

患者和对照组之间的绝对T细胞和单核细胞(亚群)计数以及单核细胞细胞因子水平相似。患者中T(h)1型细胞因子的产生高于对照组(干扰素-γ,p = 0.01;白细胞介素-2,p = 0.05),而T(h)2型细胞因子水平相当(白细胞介素-4,p = 0.5;白细胞介素-13,p = 0.3)。T细胞CD4(+)/CD8(+)比值随着pTNM分期的恶化而降低(I/II期与III/IV期相比,p = 0.009)。在所有测量的免疫参数中,只有白细胞介素-2的产生对总生存率(p = 0.015)和无病生存率(p = 0.0062)均有显著影响。高白细胞介素-2水平与良好的预后相关。

结论

与健康志愿者相比,等待食管或食管胃交界腺癌手术的患者表现出T(h)1/T(h)2平衡向有利于T(h)1的方向转变。T细胞产生白细胞介素-2的能力与生存率相关,表明T(h)1型细胞在抗肿瘤免疫监视中起关键作用。

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