乳腺癌患者血清单核细胞趋化蛋白-1水平、临床预后因素与HER-2/neu疫苗相关免疫之间的相关性

Correlations between serum monocyte chemotactic protein-1 levels, clinical prognostic factors, and HER-2/neu vaccine-related immunity in breast cancer patients.

作者信息

Dehqanzada Zia A, Storrer Catherine E, Hueman Matthew T, Foley Rebecca J, Harris Katie A, Jama Yusuf H, Kao Tzu-Cheg, Shriver Craig D, Ponniah Sathibalan, Peoples George E

机构信息

Clinical Breast Care Project, Department of Surgery, Walter Reed Army Medical Center, Washington, District of Columbia, USA.

出版信息

Clin Cancer Res. 2006 Jan 15;12(2):478-86. doi: 10.1158/1078-0432.CCR-05-1425.

DOI:10.1158/1078-0432.CCR-05-1425

PMID:16428490

Abstract

PURPOSE

We studied serum monocyte chemotactic protein-1 (MCP-1) levels in breast cancer patients in relationship to their clinicopathologic variables and immune response to a /neu E75 vaccine.

EXPERIMENTAL DESIGN

We measured MCP-1 levels in 32 /neu(+) breast cancer patients before and after vaccination with a /neu E75 peptide + granulocyte macrophage colony-stimulating factor vaccine. Clinical prognostic variables were collected. Vaccine-specific immunologic responses were monitored.

RESULTS

Serum MCP-1 levels >250 pg/mL (MCP-high) correlated with favorable prognostic variables. MCP-high patients compared with MCP-low (<250 pg/mL) patients showed statistically significant later onset of disease, earlier stage of disease, fewer nodal metastasis, and less chemotherapy. MCP-high patients had increased levels of preexisting immunity when compared with MCP-low patients (69% versus 21%; P = 0.02). However, MCP-low patients showed higher inducible levels of MCP-1 compared with MCP-high patients (median increase, 41% versus 0%; P = 0.001) after vaccination. Moreover, MCP-low patients with >50% increase in MCP-1 levels (response-high) had worse clinical prognostic variables compared with patients with <50% increase (response-low). Response-high patients had statistically significant more poorly differentiated tumors, later stage of disease, and higher percentage of large tumors. Patients with >30% postvaccination MCP-1 increase also showed significant increases in E75-specific CD8(+) T-cells (0.05% versus 0.38%; P = 0.03) in response to vaccination.

CONCLUSIONS

High serum MCP-1 levels in breast cancer patients correlate with favorable prognostic variables and increased preexisting /neu immunity. E75 vaccination induces the largest MCP-1 response in patients with unfavorable clinicopathologic variables. Therefore, low serum MCP-1 levels may identify patients with worse prognosis and those most likely to benefit from this vaccination.

摘要

目的

我们研究了乳腺癌患者血清单核细胞趋化蛋白-1（MCP-1）水平与其临床病理变量以及对α/neu E75疫苗免疫反应之间的关系。

实验设计

我们测量了32例α/neu(+)乳腺癌患者在接种α/neu E75肽+粒细胞巨噬细胞集落刺激因子疫苗前后的MCP-1水平。收集临床预后变量。监测疫苗特异性免疫反应。

结果

血清MCP-1水平>250 pg/mL（MCP高）与良好的预后变量相关。与MCP低（<250 pg/mL）患者相比，MCP高的患者在疾病发病时间、疾病分期、淋巴结转移数量和化疗次数方面具有统计学意义上的显著差异。与MCP低的患者相比，MCP高的患者的预先存在的免疫水平更高（69%对21%；P = 0.02）。然而，接种疫苗后，MCP低的患者与MCP高的患者相比，MCP-1的诱导水平更高（中位增加量，41%对0%；P = 0.001）。此外，与MCP-1水平增加<50%（反应低）的患者相比，MCP-1水平增加>50%（反应高）的MCP低的患者具有更差的临床预后变量。反应高的患者在统计学上具有显著更多的低分化肿瘤、疾病晚期和更高比例的大肿瘤。接种疫苗后MCP-1增加>30%的患者在对疫苗的反应中，E75特异性CD8(+) T细胞也有显著增加（0.05%对0.38%；P = 0.03）。