Tumor-derived factors impaired motility and immune functions of dendritic cells through derangement of biophysical characteristics and reorganization of cytoskeleton.
The generation and progress of tumors are accompanied with a marked suppression of human immune system. To explore the mechanisms by which tumors escape from immune recognition, we studied the influences of tumor microenvironment on differentiation of dendritic cells (DCs), which play an important role in tumor immunology, by biophysical and immunological methods. It was found that the cytokines derived from tumors caused an increase in osmotic fragility and a decrease in membrane fluidity of DCs, disordering and elevated expression levels of cytoskeleton, and changes of the gene transcriptional levels and energy status of the cells. Moreover, IL-12 production and the expression levels of some surface-marker molecules were also suppressed. These changes led to impaired capabilities of antigen uptake, cell motility and naïve T cell activation; the abnormal biophysical characteristics of DCs may be one aspect of the immune escape mechanism of tumor. These results provide insights into the importance of the reconstruction of tumor microenvironment for immunotherapy based on the anti-cancer activities of DCs.
Zeng
Zhu
Z
Department of Biophysics, Health Science Center, Peking University, Beijing, People's Republic of China.
Xu
Xiaofeng
X
Zhang
Yingyu
Y
Xing
Junjie
J
Long
Jinhua
J
Gu
Li
L
Wang
Xianwei
X
Sun
Dagong
D
Ka
Weibo
W
Yao
Weijuan
W
Wen
Zongyao
Z
Chien
Shu
S
D000199:Actins / Q000378:metabolism; D055592:Biophysical Phenomena; D001703:Biophysics; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D004705:Endocytosis / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D005453:Fluorescence; D005454:Fluorescence Polarization; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis; D019169:Jurkat Cells; D007959:Lymphocyte Culture Test, Mixed; D018613:Microscopy, Confocal; D009363:Neoplasm Proteins / Q000494:pharmacology*; D009996:Osmotic Fragility / Q000187:drug effects; D010641:Phenotype; D017550:Spectroscopy, Fourier Transform Infrared; D013347:Subcellular Fractions
D000199:Actins; D016207:Cytokines; D053762:Interleukin-12 Subunit p40; D009363:Neoplasm Proteins