Gold J E, Masters T R, Babbit B, Fine E M, Weber H N, Unger P D, Leventhal I, Zippe C D, Osband M E
Division of Haematology, Mount Sinai Hospital, New York, NY, USA.
Br J Urol. 1995 Jul;76(1):115-22. doi: 10.1111/j.1464-410x.1995.tb07843.x.
To determine if cis-diamminedichloroplatinum(II) (CDDP) enhances, by immunomodulation, ex vivo anti-tumour cytotoxicity of autolymphocyte therapy (ALT) against a chemotherapy-resistant tumour, and if lysis is mediated through T-cells, NK-cells, or both.
Human renal cell carcinoma (RCC) target cells were derived from surgical specimens and incubated in complete medium (CM) with CDDP, or in CM alone (control group). ALT-cells were prepared from autologous whole peripheral blood mononuclear cells (PBMC) or NK-cell (CD56)-depleted PBMC obtained before surgery. Tumour cells from each group were labelled with chromium-51(51Cr) and used as targets for ALT-cells and PBMC in a standard (4 h) and delayed (18 h) 51Cr-release assay at varying effector/target ratios (E:T).
Tumour cells incubated in CDDP showed enhanced lysis, as measured by the 51Cr-release assay, at all E:T tested. This lysis was significantly greater during the 18 h assay and when ALT-cells were used as the effector cells rather than PBMC. Depletion of CD45RO+ (memory) T-cells from the ALT cell population precluded both the 4 and 18 h tumour cell lysis. Depletion of NK-cells (CD56+) diminished the ex vivo lysis of autologous targets during the 4 but not the 18 h assay. ALT-cells derived from two patients demonstrated ex vivo tumour-specificity against autologous and allogeneic RCC.
These data suggest that: (i) ex vivo activated memory T-cells are the principal component demonstrating significant tumour-specific cytotoxicity of ALT-cells against RCC tumour targets; (ii) CDDP may alter the physical properties of tumour cells rendering them susceptible to immune-mediated attack; (iii) the combination of ALT and CDDP may lead to increased therapeutic efficacy in patients with metastatic RCC.
确定顺二氯二氨铂（II）（CDDP）是否通过免疫调节增强自体淋巴细胞疗法（ALT）对化疗耐药肿瘤的体外抗肿瘤细胞毒性，以及细胞溶解是否通过T细胞、NK细胞或两者介导。
人肾细胞癌（RCC）靶细胞取自手术标本，在完全培养基（CM）中与CDDP一起孵育，或仅在CM中孵育（对照组）。ALT细胞由术前获得的自体全外周血单个核细胞（PBMC）或NK细胞（CD56）耗尽的PBMC制备。每组肿瘤细胞用铬-51（51Cr）标记，并在不同效应细胞/靶细胞比例（E:T）下用于标准（4小时）和延迟（18小时）51Cr释放试验中的ALT细胞和PBMC的靶细胞。
通过51Cr释放试验测量，在所有测试的E:T下，在CDDP中孵育的肿瘤细胞显示出增强的细胞溶解。在18小时试验期间以及当ALT细胞用作效应细胞而非PBMC时，这种细胞溶解明显更大。从ALT细胞群体中耗尽CD45RO +（记忆）T细胞可排除4小时和18小时的肿瘤细胞溶解。NK细胞（CD56 +）的耗尽在4小时试验期间但不在18小时试验期间减少了自体靶标的体外细胞溶解。来自两名患者的ALT细胞显示出对自体和同种异体RCC的体外肿瘤特异性。
这些数据表明：（i）体外激活的记忆T细胞是显示ALT细胞对RCC肿瘤靶标具有显著肿瘤特异性细胞毒性的主要成分；（ii）CDDP可能改变肿瘤细胞的物理性质，使其易受免疫介导的攻击；（iii）ALT和CDDP的组合可能导致转移性RCC患者的治疗效果增加。
