Selection of CD8+PD-1+ lymphocytes in fresh human melanomas enriches for tumor-reactive T cells.
Selection of CD8+PD-1+ lymphocytes in fresh human melanomas enriches for tumor-reactive T cells.
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DOI：
10.1097/cji.0b013e3181fad2b0
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发表时间：
2010-11
期刊：
影响因子：
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通讯作者：
Yang JC
中科院分区：
文献类型：
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作者：
Inozume T;Hanada K;Wang QJ;Ahmadzadeh M;Wunderlich JR;Rosenberg SA;Yang JC
人黑色素瘤中的CD 8+肿瘤浸润淋巴细胞（TIL）表达高水平的PD-1并且功能受损。然而，使用体外扩增的TIL的过继细胞疗法可以是晚期黑色素瘤患者的高效疗法。这种差异导致我们进一步分析CD 8 +PD-1+ TIL。我们发现，在IL-2中体外培养后产生肿瘤反应性TIL的肿瘤细胞中，表达PD-1的CD 8 + T细胞的百分比较高（P=0.0007）。与CD 8 + PD-1-T细胞相比，肿瘤细胞中分选和扩增的CD 8 +PD-1+ T细胞也显示出高得多的肿瘤特异性IFN-γ产生。这些结果表明，黑色素瘤肿瘤细胞中的肿瘤特异性CD 8 + T细胞主要是PD-1+，并且该群体在IL-2中培养后可以恢复功能。PD-1已被报道为T细胞上的抑制性受体。我们发现，来自黑素瘤上的天然PD-L1表达水平的培养的TIL的体外功能抑制是最小的，而且在培养期间，CD 8+肿瘤特异性TIL上的PD-1表达水平降低。因此，PD-1受体可以是用于从新鲜黑素瘤富集肿瘤特异性T细胞的有用生物标志物。
CD8+ Tumor infiltrating lymphocyte (TIL) in human melanomas express high levels of PD-1 and are functionally impaired. However, adoptive cell therapy using in vitro-expanded TIL can be a highly effective therapy for patients with advanced melanoma. This discrepancy led us to further analyze the CD8+PD-1+ TILs. We found that the percentage of PD-1 expressing CD8+ T-cells was higher in the tumor digests that generate tumor-reactive TILs after in vitro culture in IL-2 (P=0.0007). Also sorted and expanded CD8+PD-1+ T-cells in tumor digests showed much higher tumor specific IFN-γ production compared with CD8+PD-1- T-cells. These results suggested that tumor-specific CD8+ T-cells in melanoma tumor digests are largely PD-1+, and this population can recover function after culturing in IL-2. PD-1 has been reported as an inhibitory receptor on T-cells. We found that the in vitro functional suppression of cultured-TILs from native levels of PD-L1 expression on melanomas was minimal, and moreover expression level of PD-1 on CD8+ tumor-specific TILs decreased during the culture. As a consequence, the PD-1 receptor can be a useful biomarker for enriching tumor specific T-cells from fresh melanomas.