TLR4 signaling promotes immune escape of human lung cancer cells by inducing immunosuppressive cytokines and apoptosis resistance
Authors: Weigang He
Qiuyan Liu
Nan Li
Xuetao Cao
Li Wang
Wei Chen
Journal: Molecular Immunology (2007)
Discipline: IMMUNOLOGY
Keywords: Tumors; immunosuppressive cytokines; chronic inflammation; Toll-like receptors (TLRs); human lung cancer cells
Affiliations: Institute of Immunology and National Key Laboratory of Medical Immunology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, PR China.

Abstract:  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. 

Retracted: No

PubPeer comments:
 Six panels in Figure 3B appear to look very similar to panels in Figure 6. Panels appear to show different experiments, except maybe for the one marked in green. Resolution compression is different between the two figures, so these similarities are not on pixel level and are best appreciated if looking on a small screen or from a distance. I have circled some groups of events that look similar to help guide the eye. ![file] , 
 Fig 4A, 4B. ![file] What appears to be the same Actin band is the loading control for H1299 cells, exposed to LPS for 0 10 20 30 60 240 minutes; and for the cytoplasmic fraction of H1299 cells, exposed for 0 10 30 60 120 240 minutes. I am also concerned by the similarity of the t-p38 band for A549 cells, and the NuP62 loading control for the nuclear fraction of H1299 cells. , 
 An additional finding in Figure 4A, highlighted in pink. The p-JNK and t-JNK panels look very similar to each other, although they have been shifted one lane. Could the authors please check? ![file] , 
 Corrigendum, May 2020: https: www.sciencedirect.com science article pii S016158902030345X  The authors regret that there are some mistakes in Figs. 4A, B and 6 on page 2855 and 2857. The correct Figs. 4A, B and 6 are presented below. The correction will not affect the result and scientific conclusion of the manuscript. The authors would like to apologise for any inconvenience caused. This is a corrigendum to address - what appears to be - type III duplications in Flow Cytometry plots. ,