Expression and activity of signaling molecules in T lymphocytes obtained from patients with metastatic melanoma before and after interleukin 2 therapy.
Expression and activity of signaling molecules in T lymphocytes obtained from patients with metastatic melanoma before and after interleukin 2 therapy.
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白细胞介素 2 治疗前后转移性黑色素瘤患者 T 淋巴细胞中信号分子的表达和活性。
DOI：
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发表时间：
1996
影响因子：
11.5
通讯作者：
T. Whiteside
中科院分区：
文献类型：
--
作者：
H. Rabinowich;Michael Banks;Torsten E. Reichert;Theodore F. Logan;J. M. Kirkwood;T. Whiteside
最近的研究表明，癌症患者T细胞和自然杀伤细胞中信号分子的表达和功能发生了变化。晚期癌症患者免疫细胞功能受损可能是由于信号转导缺陷所致。我们研究了从45例晚期转移性黑色素瘤患者的外周血或肿瘤相关淋巴结(LN)中获得的纯化T细胞是否存在各种信号分子的异常表达或活性。Western印迹分析显示CD3-Zeta在11份T细胞制剂中有10份表达降低，这些T细胞来自肿瘤相关的淋巴结。通过对黑色素瘤组织冰冻切片进行原位免疫染色，CD3-Zeta的表达也显示出类似的减少。与正常人相比，这些患者的T细胞中p56(Lck)和ZAP-70的表达减少，但磷脂酶C-Gamma1的表达不减少。在50%的患者中，CD3-Zeta和p56(Lck)在肿瘤累及的LNS和外周血中的T淋巴细胞中的表达均降低。为了确定这些信号分子的表达缺陷是否可逆，来自黑色素瘤LN的T细胞在白介素2(IL-2)的存在下孵育48h，并比较新鲜或培养淋巴细胞的裂解物信号分子表达的变化。在IL-2存在下培养的细胞CD3-Zeta和p56(Lck)表达增加，接近正常T细胞水平。然而，在IL-2存在下培养的任何LN来源的淋巴细胞中，p56(Lck)激酶的活性水平都没有恢复正常。对于治疗无效的转移性黑色素瘤患者，低剂量或高剂量的IL-2免疫治疗不能逆转患者T细胞CD3-Zeta或p56(Lck)表达的下降。然而，在三名取得临床反应的患者中，在IL-2治疗后，外周血T细胞中Zeta的最初降低表达恢复正常。
Recent studies have demonstrated altered expression and function of signaling molecules in T and natural killer cells in patients with cancer. The impairment of immune cell functions in advanced cancer may result from defects in signal transduction. We studied purified T cells obtained from peripheral blood or tumor-involved lymph nodes (LNs) of 45 patients with advanced metastatic melanoma for the presence of abnormalities in expression or activity of various signaling molecules. Western blot analyses demonstrated reduced expression of CD3-zeta in 10 of 11 preparations of T cells obtained from tumor-involved LNs. Similar reduction in expression of CD3-zeta was demonstrated by immunostaining performed in situ on frozen sections of melanoma tissues. Expression of p56(lck) and Zap-70, but not phospholipase C-gamma1, was reduced in these patients' T cells relative to those obtained from normal individuals. In 50% of the patients, reduced expression of CD3-zeta and p56(lck) was observed in T lymphocytes obtained both from tumor-involved LNs and from peripheral blood. To determine whether deficient expression of these signaling molecules is reversible, T cells from melanoma-involved LNs were incubated in the presence of interleukin 2 (IL-2) for 48 h, and lysates from fresh or cultured lymphocytes were compared for changes in expression of signaling molecules. Cells cultured in the presence of IL-2 demonstrated increased expression of CD3-zeta and p56(lck), which approached the levels detected in normal T cells. However, the level of p56(lck) kinase activity did not normalize in any of the LN-derived lymphocytes cultured in the presence of IL-2. Decreased expression of CD3-zeta or p56(lck) observed in the patients' T cells was not reversed by immunotherapy with IL-2 at low or high dose in those patients with metastatic melanoma who failed to respond to therapy. However, in three patients who achieved clinical responses, the initially reduced expression of zeta in peripheral blood T cells normalized following IL-2 therapy.
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影响因子：
56.9
作者：
MIZOGUCHI, H;O'SHEA, JJ;OCHOA, AC
通讯作者：
OCHOA, AC
浸润性肾细胞癌的 T 细胞尽管可以产生白细胞介素 2 并表达白细胞介素 2 受体，但其增殖反应较差。
影响因子：
11.2
作者：
Alexander,JP;Kudoh,S;Melsop,KA;Hamilton,TA;Edinger,MG;Tubbs,RR;Sica,D;Tuason,L;Klein,E;Bukowski,RM
通讯作者：
Bukowski,RM
影响因子：
56.9
作者：
TOWNSEND, SE;ALLISON, JP
通讯作者：
ALLISON, JP
荷瘤小鼠巨噬细胞异常的抗原呈递参与了 T 细胞反应的下调。
DOI：
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发表时间：
1995
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Watson,GA;Lopez,DM
通讯作者：
Lopez,DM
在携带 IL-2 分泌肿瘤的小鼠中，未观察到患有亲本肿瘤的小鼠 T 细胞的异常信号转导。
DOI：
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发表时间：
1994
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Salvadori,S;Gansbacher,B;Pizzimenti,AM;Zier,KS
通讯作者：
Zier,KS