Fossati G, Balsari A, Taramelli D, Sensi M L, Pellegris G, Nava M, Parmiani G
Division of Experimental Oncology A, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Cancer Immunol Immunother. 1982;14(2):99-104. doi: 10.1007/BF00200176.
Peripheral blood lymphocytes (PBL) of melanoma patients were sensitized in vitro with lymphocytes of a single donor or with a pool of lymphocytes of 5-20 different donors. After 6-7 days, the cytotoxic activity of the sensitized PBL was tested against cultured autologous tumor cells and lymphocytes in a 51Cr-release assay. Tumor lysis was observed in 13 of 16 cases in which patients' PBL (Pt-PBL) were stimulated by a pool of allogeneic lymphocytes and in five out of seven cases when single sensitization was performed. In no case was lysis of autologous normal lymphocytes or blasts seen. Cultivation of Pt-PBL with irradiated autologous tumor cells never led to the induction of lymphocytes cytotoxic to melanoma cells. Lysability by pool-activated autologous Pt-PBL of fresh cryopreserved tumor cells was compared to that of short-term cultured tumor cells, and no significant differences were observed. Cold-target inhibition experiments indicated that the cytotoxicity of Pt-PBL was tumor-restricted since only autologous melanoma cells but not lymphocytes were able to inhibit the reaction. These results indicate that activation of Pt-PBL is necessary in order to elicit or amplify their antitumor activity.
黑色素瘤患者的外周血淋巴细胞(PBL)在体外与单个供体的淋巴细胞或5至20个不同供体的淋巴细胞混合液进行致敏。6至7天后,在51Cr释放试验中检测致敏PBL对培养的自体肿瘤细胞和淋巴细胞的细胞毒性活性。在16例患者中,有13例患者的PBL(Pt-PBL)受到同种异体淋巴细胞混合液刺激后观察到肿瘤溶解,在7例进行单个致敏的病例中有5例观察到肿瘤溶解。未观察到自体正常淋巴细胞或母细胞的溶解。用辐照的自体肿瘤细胞培养Pt-PBL从未导致诱导出对黑色素瘤细胞具有细胞毒性的淋巴细胞。将混合激活的自体Pt-PBL对新鲜冷冻保存的肿瘤细胞的可裂解性与短期培养的肿瘤细胞的可裂解性进行比较,未观察到显著差异。冷靶抑制实验表明,Pt-PBL的细胞毒性是肿瘤特异性的,因为只有自体黑色素瘤细胞而不是淋巴细胞能够抑制反应。这些结果表明,激活Pt-PBL对于引发或增强其抗肿瘤活性是必要的。