免疫评分在直肠癌患者中的预后和预测价值。

Prognostic and predictive values of the immunoscore in patients with rectal cancer.

机构信息

Authors' Affiliations: Department of Surgery, University of Medicine and Pharmacy "Gr T Popa"; Departments of Pathology and Surgical Oncology, Regional Institute of Oncology; Department of Pathology St. Spiridon Hospital, Iasi, Romania; Department of General and Digestive Surgery of the Georges Pompidou European Hospital and Department of Pathology of the Georges Pompidou European Hospital, Laboratory of Immunology, Immunomonitoring platform of the Georges Pompidou European Hospital, AP-HP; Laboratory of Integrative Cancer Immunology, Institut national de la santé et de la recherche medicale (INSERM) U872, Cordeliers Research Center; Paris-Descartes University; Pierre et Marie Curie-Paris 6 University, Paris; and Department of Pathology, Avicenne Hospital, Bobigny, France.

出版信息

Clin Cancer Res. 2014 Apr 1;20(7):1891-9. doi: 10.1158/1078-0432.CCR-13-2830.

DOI:10.1158/1078-0432.CCR-13-2830

PMID:24691640

Abstract

PURPOSE

To determine whether the tumor immune infiltrate, as recently evaluated with the Immunoscore methodology, could be a useful prognostic marker in patients with rectal cancers.

EXPERIMENTAL DESIGN

The influence of the immune infiltrate on patient's outcome was investigated in patients with or without preoperative chemoradiation therapy (pCRT). The density of total (CD3(+)) and cytotoxic (CD8(+)) T lymphocytes was evaluated by immunohistochemistry and quantified by a dedicated image analysis software in surgical specimens of patients with rectal cancer (n = 111) who did not receive pCRT and in tumor biopsies performed before pCRT from additional 55 patients. The results were correlated with tumor recurrence, patient's survival, and response to pCRT.

RESULTS

The densities of CD3(+) and CD8(+) lymphocytes and the associated Immunoscore (from I0 to I4) were significantly correlated with differences in disease-free and overall survival (HR, 1.81 and 1.72, respectively; all P < 0.005). Cox multivariate analysis supports the advantage of the Immunoscore compared with the tumor-node-metastasis (TNM) staging in predicting recurrence and survival (all P < 0.001). Lymph node ratio added information in a prognostic model (all P < 0.05). In addition, high infiltration of CD3(+) and CD8(+) lymphocytes in tumor biopsies was associated with downstaging of the tumor after pCRT (CD3(+) cells; Fisher exact test P = 0.01).

CONCLUSIONS

The Immunoscore could be a useful prognostic marker in patients with rectal cancer treated by primary surgery. The determination of the immune infiltrate in biopsies before treatment could be a valuable information for the prediction of response to pCRT.

摘要

目的

评估肿瘤免疫浸润情况（最近采用免疫评分方法评估）是否可作为直肠癌患者的有用预后标志物。

实验设计

研究免疫浸润对接受或未接受术前放化疗（pCRT）的直肠癌患者结局的影响。采用免疫组化法检测总（CD3(+)）和细胞毒性（CD8(+)）T 淋巴细胞浸润密度，并通过专用图像分析软件对未接受 pCRT 的直肠癌患者（n=111）的手术标本和另外 55 例患者 pCRT 前肿瘤活检标本中的浸润密度进行定量。结果与肿瘤复发、患者生存和 pCRT 反应相关。

结果

CD3(+)和 CD8(+)淋巴细胞密度及相关免疫评分（I0 至 I4）与无病生存和总生存差异显著相关（风险比分别为 1.81 和 1.72；均 P<0.005）。Cox 多因素分析支持免疫评分优于肿瘤-淋巴结-转移（TNM）分期，可用于预测复发和生存（均 P<0.001）。淋巴结比率在预后模型中提供了更多信息（均 P<0.05）。此外，pCRT 后肿瘤活检中 CD3(+)和 CD8(+)淋巴细胞浸润程度较高与肿瘤降期相关（CD3(+)细胞；Fisher 确切检验 P=0.01）。