TLR4 signaling promotes immune escape of human lung cancer cells by inducing immunosuppressive cytokines and apoptosis resistance.
Tumors actively develop different mechanisms such as immunosuppressive cytokine production to escape from immune control and limit the success of immunotherapy. More and more evidences suggest that chronic inflammation contributes to cancer development and progression. Recently, Toll-like receptors (TLRs), the receptors by which immune cells recognize microbial conserved components such as lipopolysaccharide (LPS) then initiate immune and inflammatory responses, have been found to be expressed by some kinds of tumor cells. However, what is the biological function of TLRs on tumor cells and whether human lung cancer cells can express TLRs remain to be fully understood. In the present study, we demonstrate that TLR4 is expressed on human lung cancer cell lines. TLR4 ligation promotes production of immunosuppressive cytokines TGF-beta, VEGF, proangiogenic chemokine IL-8 by human lung cancer cells. In addition, TLR4 ligation induces resistance of human lung cancer cells to TNF-alpha or TRAIL-induced apoptosis. Furthermore, we show p38MAPK activation is necessary for increased VEGF and IL-8 secretion, NF-kappaB activation contributes to apoptosis resistance of human lung cancer cells induced by LPS. Therefore, we demonstrate that TLR4 expressed on human lung cancer cells is functionally active, and may play important roles in promoting immune escape of human lung cancer cells by inducing immunosuppressive cytokines and apoptosis resistance.
He
Weigang
W
Institute of Immunology and National Key Laboratory of Medical Immunology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, PR China.
Liu
Qiuyan
Q
Wang
Li
L
Chen
Wei
W
Li
Nan
N
Cao
Xuetao
X
D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D006801:Humans; D007165:Immunosuppression Therapy; D007249:Inflammation; D016209:Interleukin-8 / Q000276:immunology; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*; D019139:Tumor Escape / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology
D016209:Interleukin-8; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A