肝细胞癌组织ICOS+T细胞的多重免疫组织化学检测及其预后价值研究

马家强; 曹春梅; 陈　沁; 高　强; 张晓明

doi:10.19401/j.cnki.1007-3639.2019.05.005

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肝细胞癌组织ICOS+T细胞的多重免疫组织化学检测及其预后价值研究

论著 | 更新时间：2026-01-27

- 肝细胞癌组织ICOS+T细胞的多重免疫组织化学检测及其预后价值研究
- Detection of ICOS⁺T cells by multiplex immunohistochemistry in tumor tissue and its clinical significance in hepatocellular carcinoma
- 中国癌症杂志 2019年29卷第5期页码：352-361
- 作者机构：
  
  1. 上海大学生命科学学院,上海,200444
  2. 中国科学院上海巴斯德研究所,上海,200031
  3. 复旦大学附属肿瘤医院肿瘤研究所，复旦大学上海医学院肿瘤学系,上海,200032
  4. 复旦大学附属中山医院肝脏外科,上海,200032
- 作者简介：
- 基金信息：
  
  中国科学院战略性先导科技专项（XDB29030302）;前沿科学重点研究计划前沿科学重点项目（QYZDB-SSW-SMC036）和创新交叉团队项目;国家自然科学基金（81602488）。
- DOI：10.19401/j.cnki.1007-3639.2019.05.005
  中图分类号： R735.7
- 网络出版：2019-06-03，
  
  纸质出版：2019-06-03
- 稿件说明：
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马家强，曹春梅，Shyamal Goswami,陈　沁，高　强，张晓明. 肝细胞癌组织ICOS+T细胞的多重免疫组织化学检测及其预后价值研究[J]. 中国癌症杂志, 2019, 29(5): 352-361.

马家强, 曹春梅, 陈　沁, et al. Detection of ICOS⁺T cells by multiplex immunohistochemistry in tumor tissue and its clinical significance in hepatocellular carcinoma[J]. China Oncology, 2019, 29(5): 352-361.
马家强，曹春梅，Shyamal Goswami,陈　沁，高　强，张晓明. 肝细胞癌组织ICOS+T细胞的多重免疫组织化学检测及其预后价值研究[J]. 中国癌症杂志, 2019, 29(5): 352-361. DOI： 10.19401/j.cnki.1007-3639.2019.05.005.

马家强, 曹春梅, 陈　沁, et al. Detection of ICOS⁺T cells by multiplex immunohistochemistry in tumor tissue and its clinical significance in hepatocellular carcinoma[J]. China Oncology, 2019, 29(5): 352-361. DOI： 10.19401/j.cnki.1007-3639.2019.05.005.

摘要

背景与目的：诱导共刺激分子（inducible costimulator，ICOS）属于B7-CD28免疫球蛋白超家族成员，表达于活化T细胞表面，在T细胞的激活和免疫应答中发挥重要作用；但目前对于ICOS及ICOS+ T细胞在肝细胞癌（hepatocellular carcinoma，HCC）肿瘤组织中的表达及其意义尚不清楚。该研究旨在测定ICOS、ICOS

T细胞在HCC患者肿瘤组织中的表达情况并探讨其预后价值。方法：应用组织芯片（tissue microarrays，TMAs）和多重免疫组织化学技术（multiplex immunohistochemistry，mIHC）检测2006—2007年在复旦大学附属中山医院接受手术治疗的358例原发性HCC患者肿瘤组织和癌旁组织中ICOS

细胞、ICOS

CD4

及ICOS

CD8

T细胞的浸润密度和ICOS

细胞占CD4

、CD8

T细胞的百分比。应用Kaplan-Meier法和多因素COX回归模型分析上述指标对患者预后的影响。结果：与癌旁组织相比，ICOS

细胞和ICOS

CD4

T细胞在肿瘤组织中浸润数量显著增加（P0.000 1和P=0.009 1），而ICOS

CD8

T细胞则呈相反的降低趋势（P=0.033）；在肿瘤中，ICOS

CD4

T细胞的浸润程度显著高于ICOS

CD8

T细胞。此外，ICOS

CD4

和ICOS

CD8

T细胞占各自T细胞亚群的百分比在肿瘤组织中均显著增加（P均0.000 1）。预后分析发现，肿瘤组织中ICOS

细胞、ICOS

CD4

及ICOS

CD8

T细胞浸润高的患者总生存期（overall surviva

l，OS）更长，多因素分析证实上述指标是HCC的独立预后良好因素。结论：ICOS在HCC患者的肿瘤组织中高表达，且ICOS

细胞、ICOS

CD4

及ICOS

CD8

T细胞是OS的独立预后良好因素，提示上述指标可作为新的HCC预后免疫标志物。

Abstract

Background and purpose: Inducible costimulator (ICOS) is a member of B7-CD28 immunoglobulin superfamily and expressed on the surface of activated T cells

which plays an important role in T cell activation and effector functions. However

the expression pattern and the significance of ICOS and ICOS

T cells in tumor tissue of hepatocellular carcinoma (HCC) are not defined. To this end

the current study was planned to quantitatively detect the expression of ICOS and ICOS

T cells in the tumor tissue of HCC patients and evaluate their clinical significance. Methods: Tissue microarrays (TMAs) and multiplex immunohistochemistry (mIHC) were used to detect the expression levels of ICOS

cells

ICOS+CD4

and ICOS

CD8

T cells in tumor and paracancerous tissues from HCC patients who received surgical treatment in Zhongshan Hospital

Fudan University from 2006 to 2007 (n=358). The clinical prognosis was evaluated by Kaplan-Meier analysis and COX regression analysis. Results: The densities of infiltrating ICOS

and ICOS

CD4

T cells were significantly higher in tumor tissue than in paracancerous tissue (P0.000 1 and P=0.009 1). By contrast

the density of ICOS

CD8

T cells was significantly lower in tumor tissue than in paracancerous tissue (P=0.033). Within the tumor tissue

the density of ICOS

CD4

T cells was significantly higher compared with ICOS

CD8

T cells (P0.000 1). Moreover

the frequencies of ICOS

CD4

and ICOS

CD8

T cells in tumor tissue were significantly higher compared with their counterparts in paracancerous tissue (P0.000 1). Multivariate COX r

egression analysis identified that ICOS

cells

ICOS

CD4

and ICOS

CD8

T cells were independent favorable prognostic indices for overall survival (OS). Conclusion: Tumor infiltrating ICOS

cells are greatly elevated in the tumor tissue of HCC

and their abundance is associated with prolonged OS. Thus

ICOS

cells

ICOS

CD4

and ICOS

CD8

T cells might be used as novel prognostic immune biomarkers for HCC.

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