Kohrt Holbrook E, Nouri Navid, Nowels Kent, Johnson Denise, Holmes Susan, Lee Peter P
Division of Hematology, Department of Medicine, Stanford University, Stanford, California, USA.
PLoS Med. 2005 Sep;2(9):e284. doi: 10.1371/journal.pmed.0020284. Epub 2005 Sep 6.
While lymph node metastasis is among the strongest predictors of disease-free and overall survival for patients with breast cancer, the immunological nature of tumor-draining lymph nodes is often ignored, and may provide additional prognostic information on clinical outcome.
We performed immunohistochemical analysis of 47 sentinel and 104 axillary (nonsentinel) nodes from 77 breast cancer patients with 5 y of follow-up to determine if alterations in CD4, CD8, and CD1a cell populations predict nodal metastasis or disease-free survival. Sentinel and axillary node CD4 and CD8 T cells were decreased in breast cancer patients compared to control nodes. CD1a dendritic cells were also diminished in sentinel and tumor-involved axillary nodes, but increased in tumor-free axillary nodes. Axillary node, but not sentinel node, CD4 T cell and dendritic cell populations were highly correlated with disease-free survival, independent of axillary metastasis. Immune profiling of ALN from a test set of 48 patients, applying CD4 T cell and CD1a dendritic cell population thresholds of CD4 > or = 7.0% and CD1a > or = 0.6%, determined from analysis of a learning set of 29 patients, provided significant risk stratification into favorable and unfavorable prognostic groups superior to clinicopathologic characteristics including tumor size, extent or size of nodal metastasis (CD4, p < 0.001 and CD1a, p < 0.001). Moreover, axillary node CD4 T cell and CD1a dendritic cell populations allowed more significant stratification of disease-free survival of patients with T1 (primary tumor size 2 cm or less) and T2 (5 cm or larger) tumors than all other patient characteristics. Finally, sentinel node immune profiles correlated primarily with the presence of infiltrating tumor cells, while axillary node immune profiles appeared largely independent of nodal metastases, raising the possibility that, within axillary lymph nodes, immune profile changes and nodal metastases represent independent processes.
These findings demonstrate that the immune profile of tumor-draining lymph nodes is of novel biologic and clinical importance for patients with early stage breast cancer.
虽然淋巴结转移是乳腺癌患者无病生存期和总生存期的最强预测因素之一，但肿瘤引流淋巴结的免疫特性常常被忽视，其可能为临床结局提供额外的预后信息。
我们对77例乳腺癌患者的47个前哨淋巴结和104个腋窝（非前哨）淋巴结进行了免疫组织化学分析，并进行了5年随访，以确定CD4、CD8和CD1a细胞群体的改变是否可预测淋巴结转移或无病生存期。与对照淋巴结相比，乳腺癌患者的前哨淋巴结和腋窝淋巴结中的CD4和CD8 T细胞减少。前哨淋巴结和肿瘤累及的腋窝淋巴结中的CD1a树突状细胞也减少，但在无肿瘤的腋窝淋巴结中增加。腋窝淋巴结（而非前哨淋巴结）中的CD4 T细胞和树突状细胞群体与无病生存期高度相关，独立于腋窝转移。对48例患者的测试集腋窝淋巴结进行免疫谱分析，应用从29例患者的学习集分析中确定的CD4≥7.0%和CD1a≥0.6%的CD4 T细胞和CD1a树突状细胞群体阈值，可将患者显著分层为预后良好和不良的组，优于包括肿瘤大小、淋巴结转移范围或大小在内的临床病理特征（CD4，p<0.001；CD1a，p<0.001）。此外，腋窝淋巴结CD4 T细胞和CD1a树突状细胞群体对T1（原发肿瘤大小2 cm或更小）和T2（5 cm或更大）肿瘤患者无病生存期的分层比所有其他患者特征更显著。最后，前哨淋巴结免疫谱主要与浸润性肿瘤细胞的存在相关，而腋窝淋巴结免疫谱在很大程度上独立于淋巴结转移，这增加了腋窝淋巴结内免疫谱变化和淋巴结转移代表独立过程的可能性。
这些发现表明，肿瘤引流淋巴结的免疫谱对早期乳腺癌患者具有新的生物学和临床意义。
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