title: SLC gene-modified dendritic cells mediate T cell-dependent anti-gastric             cancer immune responses in vitro.
abstract: Dendritic cells (DCs) are potent professional antigen-presenting cells (APCs) with the ability to prime naïve T cells, and play an important role in the initiation and regulation of immune responses. In this study, we constructed a recombinant adenovirus carrying the SLC gene (Ad-SLC), and detected the biological effects of Ad-SLC-modified DCs as an adjuvant for the initiation of gastric cancer immune responses. Human DCs were transfected with Ad-SLC and the recombinant adenovirus carrying the β-galactosidase gene, Ad-LacZ, respectively. Modified DCs were pulsed with the cell lysate antigen of SGC-7901 cells (a type of gastric cancer cell line) and co-cultured with autologous T cells. The T cells were harvested and incubated with SGC-7901 cells and the cytotoxic function of the T cells was detected. Based on the data, the expression of mature DC phenotypes CD83 and CCR7 was upregulated after transfection with Ad-SLC and the chemotaxis function of DCs was augmented after transfection with Ad-SLC. Moreover, the expression of RANTES in DCs was upregulated by Ad-SLC transfection, while expression levels of IL-12p70 and IL-10 were not significantly altered. When co-cultured with autologous T cells, DCs modified with the SLC gene and pulsed with SGC-7901 cell lysates significantly promoted the proliferation of autologous T cells and induced Th1 differentiation, and displayed a strong cytotoxicity to SGC-7901 cells. In conclusion, Ad-SLC promoted DC maturation, enhancing the ability of DCs for T-cell chemotaxis and T-cell stimulation, and induced specific anti-gastric cancer cellular immunity. Recombinant Ad-SLC-modified DCs may be used as an adjuvant to induce an effective anti-gastric cancer immune response.
authors.affiliation: Department of Breast and Thyroid Surgery, Chengdu Army General Hospital, Chengdu 610083, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Xue
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
authors.forename: Feng
authors.initials: F
authors.lastname: Ran
authors.forename: Xianhui
authors.initials: X
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.forename: Yanbiao
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000256:Adenoviridae; D015703:Antigens, CD / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D054421:Chemokine CCL21 / Q000235:genetics*; D018946:Chemokine CCL5 / Q000378:metabolism; D002633:Chemotaxis / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D005822:Genetic Vectors; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics; D007136:Immunoglobulins / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics*; D010641:Phenotype; D054400:Receptors, CCR7 / Q000378:metabolism; D013274:Stomach Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000502:physiology; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D054421:Chemokine CCL21; D018946:Chemokine CCL5; D007136:Immunoglobulins; D016753:Interleukin-10; D018664:Interleukin-12; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D054400:Receptors, CCR7; D000097802:CD83 Antigen; C515370:CCR7 protein, human