Prognostic effect of epithelial and stromal lymphocyte infiltration in non-small cell lung cancer
Prognostic effect of epithelial and stromal lymphocyte infiltration in non-small cell lung cancer
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DOI：
10.1158/1078-0432.ccr-08-0133
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发表时间：
2008-08-15
影响因子：
11.5
通讯作者：
Busund, Lill-Tove
中科院分区：
文献类型：
--
作者：
Al-Shibli, Khalid I.;Donnem, Tom;Busund, Lill-Tove
目的：潜在可治愈的非小细胞肺癌（NSCLC）预后指标的主要价值应是指导手术切除后的治疗。在这方面，患者在切除时的免疫状态可能是重要的，也是可测量的。免疫系统在癌症发展过程中扮演着矛盾的角色。然而，肿瘤浸润淋巴细胞的预后意义存在争议。本研究的目的是阐明上皮和间质淋巴细胞浸润在非小细胞肺癌中的预后意义。实验设计：从335例切除的I期至IIIA期非小细胞肺癌的组织微阵列中构建了具有活力和代表性的肿瘤上皮和间质区域的重复核心。免疫组化检测上皮细胞和间质细胞CD4（+）、CD8（+）和CD20（+）淋巴细胞。结果：在单变量分析中，上皮细胞CD8(+) （P = 0.023）、基质细胞CD8(+) （P = 0.002）、上皮细胞CD20(+) （P = 0.023）、基质细胞CD20(+) （P < 0.001）和基质细胞CD4(+) （P < 0.001）淋巴细胞数量的增加与疾病特异性生存率的提高显著相关。上皮CD4（+）细胞没有发现这种关系。此外，低水平的间质CD8（+）淋巴细胞浸润与血管淋巴浸润发生率增加相关（P = 0.032）。在多变量分析中，大量的间质CD8(+) （P = 0.043）和CD4(+) （P = 0.002）细胞是疾病特异性生存的独立阳性预后因素。结论：间质中CD4（+）和CD8（+）淋巴细胞的高密度是非小细胞肺癌切除术患者独立的阳性预后指标。这可能表明这些细胞在非小细胞肺癌中介导了强烈的抗肿瘤免疫反应。
Purpose: The major value of prognostic markers in potentially curable non-small cell lung cancer (NSCLC) should be to guide therapy after surgical resection. In this regard, the patients' immune status at the time of resection may be important and also measurable. The immune system has paradoxical roles during cancer development. However, the prognostic significance of tumor-infiltrating lymphocytes is controversial. The aim of this study is to elucidate the prognostic significance of epithelial and stromal lymphocyte infiltration in NSCLC. Experimental Design: Tissue microarrays from 335 resected NSCLC, stage I to IIIA were constructed from duplicate cores of viable and representative neoplastic epithelial and stromal areas. Immunohistochemistry was used to evaluate the epithelial and stromal CD4(+), CD8(+), and CD20(+) lymphocytes. Results: In univariate analyses, increasing numbers of epithelial CD8(+) (P = 0.023), stromal CD8(+) (P = 0.002), epithelial CD20(+) (P = 0.023), stromal CD20(+) (P < 0.001), and stromal CD4(+) (P < 0.001) lymphocytes correlated significantly with an improved disease-specific survival. No such relation was noted for epithelial CD4(+) cells. Furthermore, a low level of stromal CD8(+) lymphocyte infiltration was associated with an increased incidence of angiolymphatic invasion (P = 0.032). In multivariate analyses, a high number of stromal CD8(+) (P = 0.043) and CD4(+) (P = 0.002) cells were independent positive prognostic factors for disease-specific survival. Conclusions: High densities of CD4(+) and CD8(+) lymphocytes in the stroma are independent positive prognostic indicators for resected NSCLC patients. This may suggest that these cells are mediating a strong antitumor immune response in NSCLC.