Lee R S, Schlumberger M, Caillou B, Pages F, Fridman W H, Tartour E
Laboratoire d'Immunologie Clinique, Unité INSERM 255 Institut Curie, Paris, France.
Eur J Cancer. 1996 Jun;32A(7):1233-9. doi: 10.1016/0959-8049(96)00017-2.
The natural history of thyroid tumours and the hyper-reactivity of the immune system in patients with thyroid cancer suggest that immune surveillance may play a role in the control of this disease. A study was therefore undertaken to analyse the phenotypic and functional features of tumour-infiltrating lymphocytes (TILs) derived from thyroid tumours. In a series of experiments, it was found that, in contrast to TILs derived from patients with melanoma or renal cell carcinoma, thyroid TILs could be efficiently expanded in vitro only in the presence of allogeneic EBV transformed B (B. EBV) cells. Indeed, only one of the seven thyroid-derived TILs grew in vitro without feeder cells, whereas all 16 thyroid-derived TILs could be expanded in the presence of allogeneic B. EBV feeder cells. Phenotypic analysis of these TILs revealed a frequent in vitro expansion of an unusual T cell population that expressed both the CD4 and CD8 markers. Indeed, it was demonstrated that in five of 14 TILs in short-term culture (< day 23) and four of 11 TILs in long-term culture (> day 40), a lymphocyte population that coexpressed CD4 and CD8 antigen accounted for more than 15% of the total TIL population. This double-positive T cell population was not observed in TILs derived from melanoma or renal cell carcinoma. Thyroid-derived TILs also displayed an intense cytolytic activity against NK-sensitive tumour targets with 10 of 11 TILs exhibiting significant cytotoxicity towards the NK-sensitive K562 cell line. Six of 11 TILs were also cytotoxic towards autologous tumour, but when cold target inhibition with K562 was performed with three cultures, unlabelled K562 completely inhibited lysis of autologous tumour cells. A significant expansion of CD3+CD56+ T cells in the different TIL populations may explain this high level of NK-like cytotoxicity. In conclusion, TILs derived from thyroid tumours could be efficiently expanded in vitro under certain culture conditions. Different strategies must be explored to enhance their specific tumour autologous specificity, however, before they can be used in immunotherapy protocols.
甲状腺肿瘤的自然病史以及甲状腺癌患者免疫系统的高反应性表明，免疫监视可能在该疾病的控制中发挥作用。因此，开展了一项研究来分析源自甲状腺肿瘤的肿瘤浸润淋巴细胞（TILs）的表型和功能特征。在一系列实验中发现，与源自黑色素瘤或肾细胞癌患者的TILs不同，甲状腺TILs仅在同种异体EBV转化的B（B.EBV）细胞存在的情况下才能在体外有效扩增。实际上，七个源自甲状腺的TILs中只有一个在没有饲养细胞的情况下在体外生长，而所有16个源自甲状腺的TILs在同种异体B.EBV饲养细胞存在的情况下都能扩增。对这些TILs的表型分析显示，一种同时表达CD4和CD8标志物的异常T细胞群体在体外频繁扩增。确实，已证明在短期培养（<23天）的14个TILs中有5个以及长期培养（>40天）的11个TILs中有4个，共表达CD4和CD8抗原的淋巴细胞群体占TILs总数的15%以上。在源自黑色素瘤或肾细胞癌的TILs中未观察到这种双阳性T细胞群体。源自甲状腺的TILs对NK敏感的肿瘤靶标也表现出强烈的细胞溶解活性，11个TILs中有10个对NK敏感的K562细胞系表现出显著的细胞毒性。11个TILs中有6个对自体肿瘤也具有细胞毒性，但在用三种培养物进行K562冷靶抑制时，未标记的K562完全抑制了自体肿瘤细胞的裂解。不同TIL群体中CD3 + CD56 + T细胞的显著扩增可能解释了这种高水平的NK样细胞毒性。总之，源自甲状腺肿瘤的TILs在特定培养条件下可在体外有效扩增。然而，在将它们用于免疫治疗方案之前，必须探索不同的策略来增强其对肿瘤自体的特异性。
