Properties of recombinant interleukin 2-cultured tumor-infiltrating lymphocytes in human lung cancer.

It is thought that TIL can be activated in vitro by rIL-2 and acquire specific anti-tumor activity. In this study, we investigated this possibility, using lymphocytes isolated from primary lung cancer tissues. In a first series of experiments, TILs and autologous PBLs from 16 patients were cultured in rIL-2 from 7 to 14 days under identical conditions, and were compared for proliferation (16 cases), cytolytic activity (11 cases), gamma interferon (IFN-gamma) production (8 cases), and phenotypes (10 cases). TILs grew in response to rIL-2 as well as PBLs. However, the induced cytolytic activity of TIL was significantly lower than that of PBL against autologous tumor cells and 2 human tumor cell lines. IL-2-mediated IFN-gamma production by TILs was also significantly lower than that of PBLs. TILs were phenotypically characterized by their high CD4/CD8 ratio and lack of Leu11-positive cells. Further investigations with 7 other cases showed that exogenous addition of IFN-gamma to rIL-2 cultures of TILs enhanced cytolytic activity in 4 cases. Our results indicate that IL-2 alone is sufficient for TILs to proliferate but not to acquire new functions (cytotoxicity and production of IFN-gamma).