Kurt R A, Urba W J, Smith J W, Schoof D D
Laboratory of Cellular Immunology, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Portland, OR, USA.
Int J Cancer. 1998 Sep 25;78(1):16-20. doi: 10.1002/(sici)1097-0215(19980925)78:1<16::aid-ijc4>3.0.co;2-#.
We examined signaling molecules of peripheral blood T lymphocytes obtained from women with breast cancer. In 6 of 14 patients, T lymphocytes displayed an impaired ability to translocate NFêB p65 (Rel-A) following activation by anti-CD3 and IL-2. This observation was made despite normal cytoplasmic levels of the Rel-A protein. We also detected abnormally low levels of the signaling molecules T-cell receptor (TCR)-zeta, ZAP-70 and p56lck in 4 of 14 breast cancer patients, i.e., defects in T-cell signaling molecules. T lymphocytes from 6 of the 14 patients also exhibited an increased expression of the dual specificity phosphatase, map kinase phosphatase-1 (MKP-1). MKP-1 inactivates MAP kinase and therefore may interfere with the activation of c-jun and c-fos. Abnormalities of I or more signaling molecules were found in 9 of 14 patients; however, only 3 patients had T cells that exhibited all 5 defects. Our data have implications for the detection of potentially dysfunctional T cells in patients with cancer. For example, the analysis of only 1 signaling molecule may allow patients with significant defects in T-cell signaling to go unnoticed. Finally, despite impaired Rel-A translocation, T cells were capable of transcribing IL-2. Impairments in the translocation of Rel-B and c-Rel further suggest that the NFKB family members Rel-A, Rel-B and c-Rel are not required for the transcription of IL-2 in the peripheral T lymphocytes of patients with breast cancer.
我们检测了从乳腺癌女性患者获取的外周血T淋巴细胞的信号分子。在14例患者中的6例中，T淋巴细胞在抗CD3和IL-2激活后显示出NF-κB p65（Rel-A）转位能力受损。尽管Rel-A蛋白的细胞质水平正常，但仍有此观察结果。我们还在14例乳腺癌患者中的4例中检测到信号分子T细胞受体（TCR）-ζ、ZAP-70和p56lck水平异常低，即T细胞信号分子存在缺陷。14例患者中的6例的T淋巴细胞还表现出双特异性磷酸酶丝裂原活化蛋白激酶磷酸酶-1（MKP-1）表达增加。MKP-1使丝裂原活化蛋白激酶失活，因此可能干扰c-jun和c-fos的激活。14例患者中的9例发现有1种或更多信号分子异常；然而，只有3例患者的T细胞表现出所有5种缺陷。我们的数据对癌症患者中潜在功能失调的T细胞的检测具有启示意义。例如，仅分析1种信号分子可能会使T细胞信号存在显著缺陷的患者未被发现。最后，尽管Rel-A转位受损，但T细胞仍能够转录IL-2。Rel-B和c-Rel转位的受损进一步表明，在乳腺癌患者外周T淋巴细胞中，NF-κB家族成员Rel-A、Rel-B和c-Rel并非IL-2转录所必需。
