Fractalkine transgene induces T-cell-dependent antitumor immunity through chemoattraction and activation of dendritic cells.
Fractalkine (FK, also called neurotactin or CX3CL1) is a CX3C chemokine that can chemoattract T lymphocytes, monocytes and NK cells. In our study, we investigated the induction of antitumor response by FK gene transfer. FK gene-modified 3LL lung carcinoma cells (3LL-FK) could both secrete soluble form and express membrane-bound form of FK. The tumor growth of 3LL-FK was decreased. Vaccination with 3LL-FK was effective in the induction of protective immunity and CTL. In vivo depletion analysis demonstrated that CD8(+) T cells are the main participating cells of the antitumor response. Obvious infiltrations of CD8(+) T cells, CD4(+) T cells and dendritic cells (DC) were observed in the tumor sites, suggesting that 3LL-FK might induce antitumor immunity through chemoattraction and activation of T cells and DC. Then we investigated the chemoattraction and activation of DC by 3LL-FK. Chemotaxis assay showed that the supernatants of 3LL-FK could chemoattract immature DC, which were found to express FK receptor CX3CR1, and the immature DC could obviously adhere to 3LL-FK. Adherence of DC to 3LL-FK resulted in phenotypic maturation and upregulated IL-12 secretion of DC, and more strong stimulation of allogeneic T-cell proliferation by DC. The increased production of IL-2 and IFNgamma in 3LL-FK tumor tissue was also observed. Our data suggested that FK gene transfer to tumor cells could induce T-cell-dependent antitumor immunity through chemoattraction and activation of DC.
Guo
Jun
J
Institute of Immunology, Second Military Medical University, Shanghai, PR China.
Zhang
Minghui
M
Wang
Baocheng
B
Yuan
Zhenglong
Z
Guo
Zhenhong
Z
Chen
Taoyong
T
Yu
Yizhi
Y
Qin
Zhihai
Z
Cao
Xuetao
X
D000818:Animals; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D000073883:CX3C Chemokine Receptor 1; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000276:immunology*; D002448:Cell Adhesion; D054422:Chemokine CCL22; D054428:Chemokine CX3CL1; D019742:Chemokines, CC / Q000378:metabolism; D020523:Chemokines, CX3C / Q000235:genetics* / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D015552:Injections, Intralesional; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology; D015847:Interleukin-4 / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D018121:Receptors, Cytokine / Q000378:metabolism; D015728:Receptors, HIV / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D019076:Transgenes
D000073883:CX3C Chemokine Receptor 1; C515483:Ccl22 protein, mouse; D054422:Chemokine CCL22; D054428:Chemokine CX3CL1; D019742:Chemokines, CC; D020523:Chemokines, CX3C; C515539:Cx3cl1 protein, mouse; D017931:DNA Primers; D007376:Interleukin-2; D008565:Membrane Proteins; D018121:Receptors, Cytokine; D015728:Receptors, HIV; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor