title: Toll-like receptor 4 is required for the cytotoxicity of cytokine-induced killer cells.
abstract: Cytokine-induced killer (CIK) cells are heterogeneous effector T cells with diverse T-cell receptor specificities with non-major histocompatibility complex-restricted cytolytic activities against tumor cells and are considered a promising therapeutic approach against hematologic malignancy. Recently, it has been reported that IL-15-activated CIK cells are superior to cells generated according to the standard protocol; however, the underlying mechanism remains to be elucidated. In the present study, we found that in IL-15-stimulated CIK cells, Toll-like receptor 4 (TLR4) expression was upregulated. Upon knockdown of TLR4, the cytolytic activity was considerably compromised. Re-expression of TLR4 in CIK cells restored their function, confirming the essential role of TLR4 in CIK cell cytotoxicity. Collectively, our study demonstrated that TLR4 was essential for the cytotoxicity of CIK cells against tumor cells, which might provide a novel approach to promote the therapeutic efficacy of CIK cells against hematologic malignancy.
authors.affiliation: Department of Orthopedics, Third Affiliated Hospital of Wenzhou Medical University, Rui'an, China.
authors.forename: Chunyuan
authors.initials: C
authors.lastname: Cai
authors.forename: Weibo
authors.initials: W
authors.lastname: Chen
authors.forename: Daoyi
authors.initials: D
authors.lastname: Miao
authors.forename: Li
authors.initials: L
authors.lastname: Cheng
authors.forename: Guojing
authors.initials: G
authors.lastname: Yang
authors.forename: Linzhou
authors.initials: L
authors.lastname: Zhang
authors.forename: Yongjiang
authors.initials: Y
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
mesh_terms: D002460:Cell Line; D055612:Cytokine-Induced Killer Cells / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D055785:Gene Knockdown Techniques; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy; D006801:Humans; D007113:Immunity, Innate; D016219:Immunotherapy, Adoptive; D019409:Interleukin-15 / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis; D020014:K562 Cells; D007938:Leukemia / Q000276:immunology / Q000628:therapy; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C569274:IL15 protein, human; C508600:IL6 protein, human; D019409:Interleukin-15; D015850:Interleukin-6; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4