title: Induction of autologous tumor-specific cytotoxic T-lymphocyte activity against a human renal carcinoma cell line by B7-1 (CD8O) costimulation.
abstract: Recently mouse models have shown that expression of costimulatory molecules such as B7-1 on tumor cells can induce tumor-specific immunity, suggesting that tumor cells modified to express costimulatory molecules can be a potential tumor vaccine. To investigate the importance of B7-1 co-stimulation in induction of autologous tumor immunity in humans, we established a renal carcinoma cell line, RCC-1, from a tumor resection and studied the patient's antitumor immune responses in vitro. The RCC-1 cell line constitutively expressed major histocompatibility complex (MHC) class I, intercellular adhesion molecule (ICAM)-1, and leukocyte function-associated antigen (LFA)-3 molecules, and MHC class II molecules were induced by interferon-gamma (IFN-gamma) treatment in vitro. However, neither RCC-1- nor IFN-gamma-treated RCC-1 cells expressed B7-1, and both failed to induce T-cell proliferative responses in mixed lymphocyte and tumor cell reaction (MLTR) assays, suggesting that the costimulatory signals provided by cell adhesion molecules such as ICAM-1 and LFA-3 were not sufficient to elicit an antitumor immune response. However, on transfection of the human B7-1 into RCC-1, these cells were able to induce a significant T-cell proliferation in MLTR assays. This T-cell response could be blocked by anti-B7 mAb treatment of the tumor cells. RCC-1B7 cells also induced the generation of tumor-specific cytolytic T lymphocytes to the parent RCC-1 cells in vitro, with little nonspecific cytolysis of an unrelated RCC line, A498, or autologous phytohemagglutinin (PHA) blasts. This specific cytotoxicity could be abrogated by anti-CD8 mAb and complement treatment. In summary, our study indicates that B7-1-CD28 interaction plays a critical role in induction of autologous tumor-specific cytotoxic T lymphocytes (CTLs) in humans, suggesting that the costimulatory molecule transfected tumor cells could be useful in expanding tumor-specific autologous CTL in vitro for adoptive tumor immunotherapy.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Y C
authors.initials: YC
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Zhu
authors.forename: R
authors.initials: R
authors.lastname: McHugh
authors.forename: S D
authors.initials: SD
authors.lastname: Graham
authors.forename: C D
authors.initials: CD
authors.lastname: Hillyer
authors.forename: D
authors.initials: D
authors.lastname: Dillehay
authors.forename: K W
authors.initials: KW
authors.lastname: Sell
authors.forename: P
authors.initials: P
authors.lastname: Selvaraj
mesh_terms: D000951:Antigens, Neoplasm / Q000502:physiology; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006680:HLA Antigens / Q000096:biosynthesis; D006801:Humans; D007680:Kidney Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D008213:Lymphocyte Activation / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D015815:Cell Adhesion Molecules; D006680:HLA Antigens; D010835:Phytohemagglutinins