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Interleukin-12 augments the generation of autologous tumor-reactive CD8+ cytotoxic T lymphocytes from tumor-infiltrating lymphocytes. 1995

S Kuge, and K Watanabe, and K Makino, and Y Tokuda, and T Mitomi, and N Kawamura, and S Habu, and T Nishimura
Department of Immunology, Tokai University School of Medicine, Isehara.

Human tumor-infiltrating lymphocytes (TIL) were obtained from breast cancer, renal cancer or neuroblastoma to investigate the generation of autologous tumor-reactive CD8+ cytotoxic T lymphocytes (CTL). When TIL were cultured with interleukin (IL)-2 (100 U/ml), the growth of TIL peaked around 8-10 days after the initiation of culture. In contrast, the proliferation of TIL cultured with IL-2 plus IL-12 peaked around 4-5 days after culture and tumor cells rapidly disappeared from the culture. To determine the generation of autologous tumor-reactive CD8+ CTL, TIL-derived CD8+ T cells were separated by FACStar. Both IL-2-activated and IL-2 plus IL-12-activated TIL-CD8+ T cells showed the same level of lymphokine-activated killer activity against a variety of tumor cells. However, TIL-CD8+ T cells activated with IL-2 plus IL-12 revealed greatly augmented cytotoxicity against autologous tumor cells compared with that induced by IL-2 alone. The autologous tumor cell-killing activity of TIL-CD8+ CTL was significantly inhibited by the addition of F(ab)2 anti-CD3 monoclonal antibody, indicating that these CTL recognize autologous tumor antigen through T cell receptor. These results imply that IL-12 is a novel cytokine which facilitates the generation of autologous tumor-reactive CD8+ CTL from TIL.

UI MeSH Term Description Entries
D007376 Interleukin-2 A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes. IL-2,Lymphocyte Mitogenic Factor,T-Cell Growth Factor,TCGF,IL2,Interleukin II,Interleukine 2,RU 49637,RU-49637,Ro-23-6019,Ro-236019,T-Cell Stimulating Factor,Thymocyte Stimulating Factor,Interleukin 2,Mitogenic Factor, Lymphocyte,RU49637,Ro 23 6019,Ro 236019,Ro236019,T Cell Growth Factor,T Cell Stimulating Factor
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D016246 Lymphocytes, Tumor-Infiltrating Lymphocytes that show specificity for autologous tumor cells. Ex vivo isolation and culturing of TIL with interleukin-2, followed by reinfusion into the patient, is one form of adoptive immunotherapy of cancer. Tumor Infiltrating Lymphocyte,Tumor-Derived Activated Cell,Tumor-Derived Activated Cells,Tumor-Infiltrating Lymphocyte,Tumor-Infiltrating Lymphocytes,Activated Cell, Tumor-Derived,Activated Cells, Tumor-Derived,Infiltrating Lymphocyte, Tumor,Infiltrating Lymphocytes, Tumor,Lymphocyte, Tumor Infiltrating,Lymphocyte, Tumor-Infiltrating,Lymphocytes, Tumor Infiltrating,Tumor Derived Activated Cell,Tumor Derived Activated Cells,Tumor Infiltrating Lymphocytes
D018414 CD8-Positive T-Lymphocytes A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes. Suppressor T-Lymphocytes, CD8-Positive,T8 Cells,T8 Lymphocytes,CD8-Positive Lymphocytes,Suppressor T-Cells, CD8-Positive,CD8 Positive Lymphocytes,CD8 Positive T Lymphocytes,CD8-Positive Lymphocyte,CD8-Positive Suppressor T-Cell,CD8-Positive Suppressor T-Cells,CD8-Positive Suppressor T-Lymphocyte,CD8-Positive Suppressor T-Lymphocytes,CD8-Positive T-Lymphocyte,Cell, T8,Cells, T8,Lymphocyte, CD8-Positive,Lymphocyte, T8,Lymphocytes, CD8-Positive,Lymphocytes, T8,Suppressor T Cells, CD8 Positive,Suppressor T Lymphocytes, CD8 Positive,Suppressor T-Cell, CD8-Positive,Suppressor T-Lymphocyte, CD8-Positive,T-Cell, CD8-Positive Suppressor,T-Cells, CD8-Positive Suppressor,T-Lymphocyte, CD8-Positive,T-Lymphocyte, CD8-Positive Suppressor,T-Lymphocytes, CD8-Positive,T-Lymphocytes, CD8-Positive Suppressor,T8 Cell,T8 Lymphocyte
D018664 Interleukin-12 A heterodimeric cytokine that plays a role in innate and adaptive immune responses. Interleukin-12 is a 70 kDa protein that is composed of covalently linked 40 kDa and 35 kDa subunits. It is produced by DENDRITIC CELLS; MACROPHAGES and a variety of other immune cells and plays a role in the stimulation of INTERFERON-GAMMA production by T-LYMPHOCYTES and NATURAL KILLER CELLS. Edodekin Alfa,IL-12,Natural Killer Cell Stimulatory Factor,Cytotoxic Lymphocyte Maturation Factor,IL 12,IL-12 p70,IL12,Interleukin 12,Interleukin-12 p70,Interleukin 12 p70

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