PHENOTYPIC AND FUNCTIONAL-CHARACTERIZATION OF TUMOR-INFILTRATING LYMPHOCYTES DERIVED FROM THYROID-TUMORS

The natural history of thyroid tumours and the hyper-reactivity of the immune system in patients with thyroid cancer suggest that immune sur veillance 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 tumour s. In a series of experiments, it was found that, in contrast to TILs derived from patients with melanoma or renal cell carcinoma, thyroid T ILs could be efficiently expanded in vitro only in the presence of all ogeneic EBV transformed B (B. EBV) cells. Indeed, only one of the seve n thyroid-derived TILs grew in vitro without feeder cells, whereas all 16 thyroid-derived TILs could be expanded in the presence of allogene ic B. EBV feeder cells. Phenotypic analysis of these TILs revealed a f requent in vitro expansion of an unusual T cell population that expres sed 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 i n long-term culture (> day 40), a lymphocyte population that coexpress ed CD4 and CD8 antigen accounted for more than 15% of the total TIL po pulation. This double-positive T cell population was not observed in T ILs derived from melanoma or renal cell carcinoma. Thyroid-derived TIL s also displayed an intense cytolytic activity against NK-sensitive tu mour targets with 10 of 11 TILs exhibiting significant cytotoxicity to wards the NK-sensitive K562 cell line. Six of 11 TILs were also cytoto xic towards autologous tumour, but when cold target inhibition with K5 62 was performed with three cultures, unlabelled K562 completely inhib ited lysis of autologous tumour cells. A significant expansion of CD3CD56+ T cells in the different TIL populations may explain this high l evel 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 spe cific tumour autologous specificity, however, before they can be used in immunotherapy protocols. Copyright (C) 1996 Elsevier Science Ltd.