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

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Abstract
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‐γ) 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‐γ production by TILs was also significantly lower than that of PBLs. TILs were phenotypically characterized by their high CD4/CD8 ratio and lack of Leu 11‐positive cells. Further investigations with 7 other cases showed that exogenous addition of IFN‐γ 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‐γ).

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