Dunbar P R, Smith C L, Chao D, Salio M, Shepherd D, Mirza F, Lipp M, Lanzavecchia A, Sallusto F, Evans A, Russell-Jones R, Harris A L, Cerundolo V
Molecular Immunology Group Nuffield Department of Medicine, and Imperial Cancer Research Foundation, Institute of Molecular Medicine, and Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
J Immunol. 2000 Dec 1;165(11):6644-52. doi: 10.4049/jimmunol.165.11.6644.
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.
在相当一部分黑色素瘤患者中，使用HLA - A2/肽四聚体可在外周血中检测到针对黑色素瘤抗原A（26/7 - 35）表位的细胞毒性T淋巴细胞（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伤细胞，但在一些患者中，它们在体外的激活反应却减弱了。我们使用表型标志物来表征正常个体和黑色素瘤患者中的黑色素瘤抗原A四聚体阳性（melan - A tetramer(+)）细胞，并将这些标志物与CTL功能的体外检测相关联。外周血中可检测到黑色素瘤抗原A四聚体阳性细胞的黑色素瘤患者分为两组。13名患者中有7名具有CCR7(+) CD45R0(-) CD45RA(+)表型，这与一些健康对照中发现的表型相同，并且这种表型与体外对黑色素瘤抗原A肽缺乏反应相关。在其余6名患者中，黑色素瘤抗原A四聚体阳性细胞向CCR7(-) CD45R0(+) CD45RA(-)表型转变，并且体外对黑色素瘤抗原A肽的反应很容易得到证实。当检查被表达黑色素瘤抗原A的黑色素瘤细胞浸润的淋巴结时，也出现了类似的二分法。这些发现表明，黑色素瘤抗原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够在体外检测中对抗原作出反应。
