Immune dysfunction and micrometastases in women with breast cancer

Immune dysfunction and micrometastases in women with breast cancer
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DOI:
10.1007/s10549-004-7048-0
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发表时间:
2005-05-01
影响因子:
3.8
通讯作者:
Esserman, LJ
Esserman, LJ
中科院分区:
医学2区
文献类型:
--
作者:
Campbell, MJ;Scott, J;Esserman, LJ

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由T淋巴细胞产生的细胞因子对于给定免疫应答的功效是至关重要的,并且免疫应答的失调可能在癌症进展中起作用。我们评估了乳腺癌患者外周血T细胞的细胞内细胞因子谱,并探讨了这些反应与淋巴结和骨髓中癌症存在的关系。通过四色流式细胞术分析了84例患者和26例健康志愿者外周血淋巴细胞的表面标志物和细胞内细胞因子。还收集了其中一些患者的骨髓样本,并通过流式细胞术分析了上皮细胞(微转移)的存在。与健康对照组相比,乳腺癌患者中产生1型(IL-2、IFN-γ或TNF-α)和2型(IL-4)的CD 4(+)和CD 8(+)细胞的百分比显著降低。这些结果表明,这些患者的一般免疫功能障碍,而不是1型和2型细胞平衡的转变。这些失调的T细胞反应与年龄、疾病分期或淋巴结状态无关。然而,我们确实观察到骨髓中微转移的数量与T细胞反应性之间的相关性。
Cytokines produced by T lymphocytes are critical to the efficacy of a given immune response and dysregulation of immune responses may play a role in cancer progression. We assessed the intracellular cytokine profiles of T cells in the peripheral blood of women with breast cancer and explored the relationship of these responses with the presence of cancer in lymph nodes and bone marrow. Peripheral blood lymphocytes from 84 patients and 26 healthy volunteers were analyzed by 4-color flow cytometry for surface markers and for intracellular cytokines. Bone marrow samples from some of these patients were also collected and analyzed for the presence of epithelial cells (micrometastases) by flow cytometry. The percentages of both CD4(+) and CD8(+) cells producing type1 (IL-2, IFN-γ or TNF-α) and type 2 (IL-4) were significantly lower in patients with breast cancer compared to healthy controls. These results indicate a general immune dysfunction in these patients as opposed to a shift in the balance of type1 and type2 cells. These dysregulated T cell responses did not correlate with age, stage of disease, or nodal status. However, we did observe a correlation between number of micrometastases in the bone marrow and T cell responsiveness.