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应用人白细胞抗原-A2阳性(HLA-A+2)黑色素瘤病人的瘤块中分离得到的肿瘤浸润性淋巴细胞(TIL),进行HLA-A2限制性TIL抗人黑色素瘤细胞作用的研究。在实验中发现,TIL对自身和同种异体的HLA-A+2黑色素瘤细胞具有杀伤作用,而对HLA-A-2黑色素瘤细胞及HLA-A+2非黑色素瘤细胞无作用。选择重组白细胞介素4(rIL-4)+肿瘤坏死因子α(TNFα)能促进黑色素瘤细胞HLA-A2表达量,并增强TIL对瘤细胞的杀伤活性。抗CD3、抗HLA-ABC和抗HLA-A2单抗具有明显抑制TIL的抗瘤细胞活性。结果表明TIL杀伤黑色素瘤细胞依赖于T细胞受体(TCR)对瘤细胞共同抗原的识别,并有主要组织相容性复合体-Ⅰ类分子参与。
Tumor-infiltrating lymphocytes (TIL) isolated from tumor masses of patients with human leukocyte antigen-A2 positive (HLA-A+2) melanoma were used to study the effect of HLA-A2-restricted TIL against human melanoma cells. In experiments, it was found that TIL has killing effect on self and allogeneic HLA-A+2 melanoma cells, but has no effect on HLA-A-2 melanoma cells and HLA-A+2 non-melanoma cells. Selecting recombinant interleukin 4 (rIL-4) + tumor necrosis factor alpha (TNFα) can promote the expression of HLA-A2 in melanoma cells and enhance the killing activity of TIL on tumor cells. The anti-CD3, anti-HLA-ABC and anti-HLA-A2 monoclonal antibodies had significant anti-tumor activity against TIL. The results showed that TIL killing melanoma cells depended on T cell receptor (TCR) recognition of tumor cell common antigens and involved major histocompatibility complex-I molecules.