Chemoattraction, adhesion and activation of natural killer cells are involved in the antitumor immune response induced by fractalkine/CX3CL1.
Fractalkine (FK, also called neurotactin or CX3CL1) is a CX3C chemokine that can chemoattract T lymphocytes, monocytes, dendritic cells (DC) and natural killer (NK) cells. One of our previous studies demonstrated that FK in soluble form can chemoattract T cells and DC and membrane-bound FK can adhere T cells and DC. Vaccination with 3LL lung carcinoma cells gene-modified with FK (3LL-FK) induces potent antitumor CTL response. The aim of the present study is to investigate whether NK cells participate in FK-induced antitumor immunity. We found that NK activity was increased in mice inoculated with 3LL-FK and in vivo depletion of NK cells resulted in the decreased tumor growth inhibition of 3LL-FK, indicating that NK cells play an important role in the antitumor immunity induced by FK. Further studies showed 3LL-FK could chemoattract, adhere NK cells and attract more NK cells to infiltrate into tumor tissue. Incubation of NK cells with 3LL-FK could increase the cytotoxicity of NK cells against YAC-1 cells and even against NK-resistant parental 3LL cells. IL-12 production increased more significantly in the 3LL-FK tumor nodules. Taken together with CTL response induced by 3LL-FK, our data demonstrate that FK, expressed by gene-modified tumor cells, can induce potent antitumor effect through different mechanisms, one of which involves chemoattraction of NK cells into tumor sites and activation of NK cells.
Guo
Jun
J
Institute of Immunology, Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, China.
Chen
Taoyong
T
Wang
Baocheng
B
Zhang
Minghui
M
An
Huazhang
H
Guo
Zhenhong
Z
Yu
Yizhi
Y
Qin
Zhihai
Z
Cao
Xuetao
X
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D018827:Carcinoma, Lewis Lung / Q000276:immunology*; D002448:Cell Adhesion; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000235:genetics / Q000276:immunology*; D002634:Chemotaxis, Leukocyte; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D015316:Genetic Therapy; D018664:Interleukin-12 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology* / Q000502:physiology; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D014611:Vaccination
D019496:Cancer Vaccines; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; C515539:Cx3cl1 protein, mouse; D008565:Membrane Proteins; D018664:Interleukin-12