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Tumour-infiltrating lymphocytes in primary melanoma: functional consequences of differential IL-2 receptor expression.

机译:原发性黑色素瘤中的肿瘤浸润淋巴细胞:IL-2受体表达差异的功能后果。

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摘要

Tumour-infiltrating lymphocytes (TIL) have been isolated from early primary melanoma (Clark level III) and expanded in vitro using culture conditions with low concentrations of IL-2 (50 U/ml). Immediately after isolation TIL consisted of mainly CD3+ T cells, and the portion of CD56+ natural killer (NK) cells was below 20%. Fresh TIL cultures could be distinguished by CD25 expression since some contained up to 33%, others less than 5% CD25+ cells. These showed differences in subsequent development during in vitro expansion. CD25-expressing cultures remained stable in their phenotype, whereas the second TIL type showed major changes: CD3 (ca 70-30%) expression decrease, CD25 (ca 5-35%) and CD56 (ca 15-55%) expression increase. The TIL type, which remained dominated by CD3+ T cells, killed autologous tumour cells efficiently (51Cr-release greater than 30% at a E/T ratio of 20:1), which could be blocked by MoAbs against MHC class I molecules. In contrast, the other TIL type exhibited weak cytotoxicity (less than 17% 51Cr-release at an E/T ratio of 20:1) against the autologous tumour. Therefore, the expression of CD25 on freshly isolated TIL is a good marker for tumour specificity of in vitro expanded TIL.
机译:已从早期原发性黑色素瘤(克拉克III级)中分离出肿瘤浸润淋巴细胞(TIL),并在低浓度IL-2(50 U / ml)的培养条件下进行了体外扩增。分离后,TIL立即主要由CD3 + T细胞组成,而CD56 +自然杀伤(NK)细胞部分低于20%。新鲜的TIL培养物可以通过CD25表达来区分,因为有些包含多达33%的细胞,而另一些则少于5%的CD25 +细胞。这些显示了体外扩增期间后续发育的差异。表达CD25的培养物在其表型上保持稳定,而第二种TIL类型显示了主要变化:CD3(约70-30%)表达降低,CD25(约5-35%)和CD56(约15-55%)表达增加。仍然由CD3 + T细胞控制的TIL类型有效杀死了自体肿瘤细胞(在20:1的E / T比下51Cr的释放大于30%),而MoAb可以抵抗MHC I类分子。相反,另一种TIL类型对自体肿瘤的细胞毒性较弱(在E / T比为20:1时,51Cr的释放率低于17%)。因此,新鲜分离的TIL上CD25的表达是体外扩增的TIL的肿瘤特异性的良好标志。

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