Tumor-Infiltrating CD8+ Lymphocytes Predict Clinical Outcome in Breast Cancer
Tumor-Infiltrating CD8+ Lymphocytes Predict Clinical Outcome in Breast Cancer
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DOI：
10.1200/jco.2010.30.5037
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发表时间：
2011-05-20
影响因子：
45.3
通讯作者：
Green, Andrew R.
中科院分区：
文献类型：
--
作者：
Mahmoud, Sahar M. A.;Paish, Emma Claire;Green, Andrew R.
乳腺癌通常被炎性细胞浸润，特别是巨噬细胞和T淋巴细胞，但这些细胞的意义尚不清楚。这些炎性细胞的一个可能作用是它们代表针对癌的细胞介导的免疫应答。CD 8（+）淋巴细胞是已知的细胞介导免疫的关键组分。本研究的目的是探讨肿瘤浸润的CD 8（+）细胞毒性淋巴细胞在乳腺癌中的预后价值。通过对1,334例长期随访的乳腺癌患者的组织微阵列核心进行免疫组化染色，评估肿瘤浸润性CD 8（+）淋巴细胞。在肿瘤巢（肿瘤内）、肿瘤细胞邻近的基质和肿瘤细胞远处的基质中计数CD 8（+）T细胞的数量，并确定其与临床结局的关系。CD 8（+）细胞总数与肿瘤分级呈正相关（r（s）= 0.20; P <0.001），与患者诊断时的年龄、雌激素受体α（ER-α）和孕激素受体（PgR）表达呈负相关（Mann-Whitney U检验，P <0.001）。在进行单变量生存分析之前，将总患者队列随机分为两个单独的训练和验证集。在训练集中，CD 8（+）淋巴细胞总数和远端间质淋巴细胞与更好的患者生存率相关（分别为P = 0.041和P <0.001）。在多变量分析中，总CD 8（+）T细胞计数是训练集和验证集的独立预后因素。这些结果表明，肿瘤浸润性CD 8（+）T淋巴细胞具有抗肿瘤活性，可以通过其对患者生存的有利影响来判断，并可能用于乳腺癌的治疗。J Clin Oncol 29：1949-1955. (C)2011年美国临床肿瘤学会
Breast carcinomas are often infiltrated by inflammatory cells, particularly macrophages and T lymphocytes, but the significance of these cells remains unclear. One possible role of these inflammatory cells is that they represent a cell-mediated immune response against the carcinoma. CD8(+) lymphocytes are a known crucial component of cell-mediated immunity. The purpose of this study was to explore the prognostic value of tumor-infiltrating CD8(+) cytotoxic lymphocytes in breast cancer. Tumor-infiltrating CD8(+) lymphocytes were assessed by immunohistochemical staining of tissue microarray cores from 1,334 unselected breast tumors from patients with long-term follow-up. The number of CD8(+) T cells was counted in tumor nests (intratumoral), in stroma adjacent to tumor cells, and in stroma distant to tumor cells, and their relationship with clinical outcome was determined. The total number of CD8(+) cells was positively correlated with tumor grade (r(s) = 0.20; P < .001) and inversely correlated with patient's age at diagnosis, estrogen receptor-alpha (ER-alpha), and progesterone receptor (PgR) expression (Mann-Whitney U test, P < .001). The total patient cohort was randomly divided into two separate training and validation sets before performing univariate survival analysis. Total number and distant stromal CD8(+) lymphocytes were associated with better patient survival (P = .041 and P < .001, respectively) in the training set. In multivariate analysis, total CD8(+) T-cell count was an independent prognostic factor in both training and validation sets. These results suggest that tumor-infiltrating CD8(+) T lymphocytes have antitumor activity as judged by their favorable effect on patients' survival and could potentially be exploited in the treatment of breast cancer. J Clin Oncol 29:1949-1955. (C) 2011 by American Society of Clinical Oncology