评估西妥昔单抗联合化疗治疗前后肿瘤微环境中的免疫因子。

Evaluation of the immune factors in the tumor environment before and after the treatment of cetuximab combined with chemotherapy.

机构信息

Department of Medical Oncology, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China.

出版信息

World J Surg Oncol. 2013 Sep 13;11:226. doi: 10.1186/1477-7819-11-226.

DOI:10.1186/1477-7819-11-226

PMID:24028754

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3847707/

Abstract

BACKGROUND

The effect of chemotherapy combined with monoclonal antibodies (mAbs) on the immune state of the tumor environment remains unclear and controversial. The aim of this study is to examine the effect of chemotherapy combined with cetuximab (C225, an anti-EGFR mAb) on the immune state of tumor environment, and the correlation of that effect and the clinical efficacy.

METHODS

Twelve patients with colorectal cancer, who received the treatment of chemotherapy combined with C225, were enrolled in this study. The tumor specimen of the primary colorectal cancer before and after treatment was obtained. The expression of a series of immune factors (TGF-β1, CD8, IL-2, TNF-α, and VEGF) was measured by immunochemistry. The expression of these immune factors before and after treatment was compared by the Wilcoxon signed-rank test. The correlation of the change of immune parameter expression after treatment and clinical efficacy was examined by chi-square tests. The correlation of the expression of immune factors, clinical efficacy, and treatment number was examined by the Spearman's correlation analysis.

RESULTS

There was no significant difference between the expression of TGF-β1 before and after the treatment (P >0.05). The change of TGF-β1 expression after treatment significantly correlated negatively with clinical efficacy (P = 0.05). As for CD8, IL-2, VEGF, and TNF-α, there were no significant differences between the expression before and after the treatment (P >0.05), and the change of expression after treatment also did not correlate significantly with clinical efficacy (P >0.05). The change of IL-2 expression after treatment significantly correlated negatively with treatment number (correlation coefficient = -0.585, P = 0.046). The change of TGF-β1 expression after treatment significantly correlated negatively with clinical efficacy (correlation coefficient = -0.684, P = 0.014). Before treatment, the expression of TNF-α significantly correlated positively with the expression of IL-2 (correlation coefficient = 0.629, P = 0.028). After treatment, the expression of TGF-β1 significantly correlated negatively with the expression of CD8 (correlation coefficient = -0.664, P = 0.019).

CONCLUSIONS

These results suggested that, in the tumor environment, the change of immune factors after treatment of cetuximab combined with chemotherapy may be associated with clinical efficacy.

摘要

背景

化疗联合单克隆抗体（mAbs）对肿瘤微环境免疫状态的影响尚不清楚且存在争议。本研究旨在探讨化疗联合西妥昔单抗（C225，一种抗 EGFR mAb）对肿瘤微环境免疫状态的影响，以及这种影响与临床疗效的相关性。

方法

本研究纳入了 12 例接受化疗联合 C225 治疗的结直肠癌患者。分别在治疗前后获取原发结直肠肿瘤标本，采用免疫组织化学方法检测一系列免疫因子（TGF-β1、CD8、IL-2、TNF-α 和 VEGF）的表达。采用 Wilcoxon 符号秩检验比较治疗前后免疫因子的表达变化，卡方检验分析治疗后免疫参数表达变化与临床疗效的相关性，Spearman 相关分析免疫因子表达、临床疗效与治疗次数的相关性。

结果

治疗前后 TGF-β1 的表达差异无统计学意义（P＞0.05）。治疗后 TGF-β1 表达的变化与临床疗效显著负相关（P=0.05）。CD8、IL-2、VEGF 和 TNF-α 治疗前后表达差异无统计学意义（P＞0.05），治疗后表达的变化与临床疗效也无显著相关性（P＞0.05）。治疗后 IL-2 表达的变化与治疗次数显著负相关（相关系数=-0.585，P=0.046）。治疗后 TGF-β1 表达的变化与临床疗效显著负相关（相关系数=-0.684，P=0.014）。治疗前，TNF-α 的表达与 IL-2 的表达呈显著正相关（相关系数=0.629，P=0.028）。治疗后，TGF-β1 的表达与 CD8 的表达呈显著负相关（相关系数=-0.664，P=0.019）。