Tumor-infiltrating γδ T lymphocytes predict clinical outcome in human breast cancer.
Tumor-infiltrating γδ T lymphocytes predict clinical outcome in human breast cancer.
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DOI：
10.4049/jimmunol.1201892
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发表时间：
2012-11-15
期刊：
影响因子：
--
通讯作者：
Peng G
中科院分区：
文献类型：
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作者：
Ma C;Zhang Q;Ye J;Wang F;Zhang Y;Wevers E;Schwartz T;Hunborg P;Varvares MA;Hoft DF;Hsueh EC;Peng G
了解和解剖不同亚群的调节性肿瘤浸润性T淋巴细胞(TIL)在个体癌症免疫发病机制中的作用是抗肿瘤免疫治疗的一个挑战。在乳腺TIL中发现了高水平的γδ调节性T(Treg)细胞。然而，这些肿瘤内γδT细胞的临床相关性尚不清楚。在这项研究中，通过对不同癌症进展阶段患者的原发乳腺癌组织进行免疫组织化学染色，分析了γδT细胞群。对γδT细胞水平与其他预后因素和临床结果之间的相关性进行了回顾性多因素分析。我们发现γδT细胞在乳腺肿瘤部位的浸润和聚集是乳腺癌患者的普遍特征。肿瘤内γδT细胞数量与肿瘤分期、HER2表达状态、高淋巴结转移呈正相关，与乳腺癌患者的无复发生存期和总生存期呈负相关。对肿瘤浸润性γδT细胞和其他预后因素的多因素和单因素分析进一步表明，与其他已知因素相比，肿瘤内γδT细胞是评估乳腺癌严重程度的最显著的独立预后因素。乳腺癌组织中瘤内γδT细胞与FoxP3+、CD4+T细胞呈正相关，与CD8+T细胞呈负相关。这些发现表明，肿瘤内的γδT细胞可能是一种有价值的独立的预后生物标志物，也是人类乳腺癌潜在的治疗靶点。
Understanding and dissecting the role of different subsets of regulatory tumor-infiltrating T lymphocytes (TILs) in the immunopathogenesis of individual cancer is a challenge for anti-tumor immunotherapy. High levels of γδ regulatory T (Treg) cells have been discovered in the breast TILs. However, the clinical relevance of these intra-tumoral γδ T cells is unknown. In this study, γδ T cell populations were analyzed by performing immunohistochemical staining in primary breast cancer tissues from patients with different stages of cancer progression. Retrospective multivariate analyses of the correlations between γδ T cell levels and other prognostic factors and clinical outcomes were completed. We found that γδ T cell infiltration and accumulation in breast tumor sites was a general feature in breast cancer patients. Intra-tumoral γδ T cell numbers were positively correlated with advanced tumor stages, HER2 expression status and high lymph node metastasis, but inversely correlated with relapse-free survival (RFS) and overall survival (OS) of breast cancer patients. Multivariate and univariate analyses of tumor-infiltrating γδ T cells and other prognostic factors further suggested that intra-tumoral γδ T cells were the most significant independent prognostic factor for assessing severity of breast cancer, compared with the other known factors. Intra-tumoral γδ T cells were positively correlated with FoxP3+ cells and CD4+ T cells, but negatively correlated with CD8+ T cells in breast cancer tissues. These findings suggest that intra-tumoral γδ T cells may serve as a valuable and independent prognostic biomarker, as well as a potential therapeutic target for human breast cancer.