A shift in the phenotype of melan-A-specific CTL identifies melanoma patients with an active tumor-specific immune response
A shift in the phenotype of melan-A-specific CTL identifies melanoma patients with an active tumor-specific immune response
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DOI：
10.4049/jimmunol.165.11.6644
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发表时间：
2000-12-01
影响因子：
4.4
通讯作者：
Cerundolo, V
中科院分区：
文献类型：
--
作者：
Dunbar, PR;Smith, CL;Cerundolo, V
在很大比例的黑色素瘤患者中，可以使用HLA-A2/肽四聚体在外周血中检测到针对黑色素瘤a（26/7-35）表位的CTL。然而，这些CTL的功能能力一直存在争议，因为尽管它们在体外扩增后被证明是有效的杀手，但在一些患者中，它们在体外会减弱激活反应。我们使用表型标记来表征正常个体和黑色素瘤患者的黑色素- a四聚体（+）细胞，并将这些标记与体外CTL功能测定相关联。黑色素瘤患者可检测到黑色素- a四聚体（+）。外周血细胞分为两组。13例患者中有7例具有CCR7(+) CD45R0(-) CD45RA（+）表型，与一些健康对照相同，并且这种表型与体外对黑色素- a肽缺乏反应有关。在其余6例患者中，黑色素- a四聚体+细胞转变为CCR7(-) CD45R0(+) CD45RA（-）表型，并且对黑色素- a肽的反应可以很容易地在体外证明。当淋巴结浸润表达黑色素瘤细胞黑色素瘤检查，类似的二分法出现。这些发现表明，黑色素瘤a特异性CTL的激活仅发生在一些恶性黑色素瘤患者中，并且只有具有这种活跃免疫反应的患者才能在离体试验中对Ag有反应。
In a significant proportion of melanoma patients, CTL specific for the melan-A(26/7-35) epitope can be detected in peripheral blood using HLA-A2/peptide tetramers, However, the functional capacity of these CTL has been controversial, since although they prove to be effective killers after in vitro expansion, in some patients they have blunted activation responses ex vivo. We used phenotypic markers to characterize melan-A tetramer(+) cells in both normal individuals and melanoma patients, and correlated these markers with ex vivo assays of CTL function. Melanoma patients with detectable melan-A tetramer(+). cells in peripheral blood fell into two groups. Seven of thirteen patients had a CCR7(+) CD45R0(-) CD45RA(+) phenotype, the same as that found in some healthy controls, and this phenotype was associated with a lack of response to melan-A peptide ex vivo. In the remaining six patients, melan-A tetramer+ cells were shifted toward a CCR7(-) CD45R0(+) CD45RA(-) phenotype, and responses to melan-A peptide could be readily demonstrated ex vivo. When lymph nodes infiltrated by melan-A-expressing melanoma cells were examined, a similar dichotomy emerged. These findings demonstrate that activation of melan-A-specific CTL occurs in only some patients with malignant melanoma, and that only patients with such active immune responses are capable of responding to Ag in ex vivo assays.