Lysis by interleukin 2-stimulated tumor-infiltrating lymphocytes of autologous and allogeneic tumor target cells

Abstract

Peripheral blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) were isolated from six cancer patients and cultured in the presence of 100 units/ml of recombinant interleukin 2 (IL2). Both IL2-stimulated PBL (IL2-PBL) and IL2-stimulated TIL (IL2-TIL) lysed fresh and short-term cultured autologous tumor cells in four and six cases, respectively. In four out of six patients IL2-TIL showed a slightly higher tumor cytotoxicity than IL2-PBL without lysing autologous normal PBL or TIL. Like IL2-PBL, IL2-TIL also killed allogeneic fresh and cultured targets of different histotypes, suggesting a lack of autologous tumor cytotoxic specificity. TIL cultured for 3 weeks in IL2 maintained their killing activity against autologous and allogeneic tumor targets. Phenotypic analysis of uncultured TIL showed a predominance of CD3⁺ T cells (∼70%) with CD4⁺ (∼60%) and CD8⁺ (20%) lymphocyte subsets, whereas ≤3% of CD16⁺ natural killer cells were present. TIL but not PBL contained 12%–19% of lymphocytes which expressed activation markers such as DR and TAC. The culture of both TIL and PBL in IL2 for 2–3 weeks induced an increase in the percentage of CD8⁺ and a decrease in CD4⁺ and augmentation of Leu 19⁺, DR⁺, and TAC⁺ cells. These results indicate that IL2-TIL can lyse autologous tumor cells slightly better than IL2-PBL, although such an effect was also evident against allogeneic neoplastic targets.