title: TLR4 plays a crucial role in MSC-induced inhibition of NK cell function.
abstract: Mesenchymal stem cells (MSC) are a kind of stromal cell within the tumor microenvironment. In our research, MSC derived from acute myeloid leukemia patients' bone marrow (AML-MSC) and lung cancer tissues (LC-MSC) as well as normal bone marrow-derived MSC (BM-MSC) cultured in conditioned medium of HeLa cells were found to have higher expressions of Toll-like receptor (TLR4) mRNA compared with BM-MSC. The sorted TLR4-positive MSC (TLR4+ MSC) differed in cytokine (interleukin-6, interleukin-8, and monocyte chemoattractant protein-1) secretion from those of unsorted MSC. MSC was reported to inhibit natural killer (NK) cell proliferation and function. In this research, we confirmed that TLR4+ MSC aggravate this suppression. Furthermore, when TLR4 in the sorted cells were stimulated by LPS or following blocked by antibody, the suppression on NK cell proliferation and cytotoxicity were more intensive or recovered respectively. Compared to unsorted MSC, NKG2D receptor expression on NK cells were also inhibited by TLR4+ MSC. These findings suggest that activation of TLR4 pathway is important for TLR4+ MSC and MSC to obstruct anti-tumor immunity by inhibiting NK cell function, which may provide a potential stroma-targeted tumor therapy.
authors.affiliation: No. 307 Hospital of the Chinese People's Liberation Army, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Yaru
authors.initials: Y
authors.lastname: Qin
authors.affiliation: No. 307 Hospital of the Chinese People's Liberation Army, Beijing, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Luo
authors.affiliation: No. 307 Hospital of the Chinese People's Liberation Army, Beijing, China. Electronic address: 13691110351@163.com.
authors.forename: Quanli
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China. Electronic address: duanhf0720@163.com.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Duan
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005260:Female; D006367:HeLa Cells; D006801:Humans; D016130:Immunophenotyping; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051197:Toll-Like Receptor 4 / Q000502:physiology*; D059016:Tumor Microenvironment
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
keywords: Anti-tumor immunity; MSC; NK cells; TLR4