Tumor transfected with CCL21 enhanced reactivity and apoptosis resistance of human monocyte-derived dendritic cells.
Chemokine CCL21 can effectively attract CCR7(+) dendritic cells (DCs), however its role in this event is poorly understood. In this report, we investigated the effect of exogenous CCL21 expressed in breast cancer MCF-7 on human monocyte-derived DCs. CCL21-transfected MCF-7 stimulation prompted DC functions: migration, antigen-uptake and presentation. The stimulated DCs facilitated Th1 type cytokines production, perforin-forming CD8(+) T cell transformation and final T cell-associated clearance of MCF-7. Moreover, the MCF-7-resourced CCL21 protected DCs from apoptosis significantly, involving up-regulations of Bcl-2 expression and NF-kappaB activity, and reduction of caspase-3. This study provides evidence that tumor-derived CCL21 increases the presentation and apoptosis resistance of DCs, suggesting such a mechanism may be useful for the improvement of tumor cell immunogenicity and anti-tumor response.
Wu
Sha
S
Department of Immunology, Basic Medicine Institute, Tongji Medical College, Huazhong University of Science and Technology, No. 13 Hangkong Road, Wuhan 430030, People's Republic of China.
Xing
Wei
W
Peng
Jiling
J
Yuan
Xiaomei
X
Zhao
Xiaoping
X
Lei
Ping
P
Li
Wenhan
W
Wang
Min
M
Zhu
Huifen
H
Huang
Bo
B
Huang
Liming
L
Shen
Guanxin
G
D000328:Adult; D017951:Antigen Presentation / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D001943:Breast Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D054421:Chemokine CCL21 / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D014162:Transfection
D054421:Chemokine CCL21