Lysis by interleukin 2-stimulated tumor-infiltrating lymphocytes of autologous and allogeneic tumor target cells.
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 (approximately 70%) with CD4+ (approximately 60%) and CD8+ (20%) lymphocyte subsets, whereas less than or equal to 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.
Radrizzani
M
M
Division of Experimental Oncology D, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Gambacorti-Passerini
C
C
Parmiani
G
G
Fossati
G
G
D002460:Cell Line; D002465:Cell Movement; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000032:analysis; D006801:Humans; D007376:Interleukin-2; D008214:Lymphocytes / Q000145:classification / Q000276:immunology*; D010641:Phenotype; D014407:Tumor Cells, Cultured / Q000276:immunology*
D000939:Epitopes; D007376:Interleukin-2