title: Inhibitory leukocyte immunoglobulin-like receptors in cancer development.
abstract: Inhibitory leukocyte immunoglobulin-like receptors (LILRB1-5) signal through immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in their intracellular domains and recruit phosphatases protein tyrosine phosphatase, non-receptor type 6 (PTPN6, SHP-1), protein tyrosine phosphatase, non-receptor type 6 (PTPN6, SHP-2), or Src homology 2 domain containing inositol phosphatase (SHIP) to negatively regulate immune cell activation. These receptors are known to play important regulatory roles in immune and neuronal functions. Recent studies demonstrated that several of these receptors are expressed by cancer cells. Importantly, they may directly regulate development, drug resistance, and relapse of cancer, and the activity of cancer stem cells. Although counterintuitive, these findings are consistent with the generally immune-suppressive and thus tumor-promoting roles of the inhibitory receptors in the immune system. This review focuses on the ligands, expression pattern, signaling, and function of LILRB family in the context of cancer development. Because inhibition of the signaling of certain LILRBs directly blocks cancer growth and stimulates immunity that may suppress tumorigenesis, but does not disturb normal development, LILRB signaling pathways may represent ideal targets for treating hematological malignancies and perhaps other tumors.
authors.affiliation: Hongqiao International Institute of Medicine, Shanghai Tongren Hospital; Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.|Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
authors.forename: FeiFei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Hongqiao International Institute of Medicine, Shanghai Tongren Hospital; Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. zhengjunke@sjtu.edu.cn.|Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. zhengjunke@sjtu.edu.cn.
authors.forename: JunKe
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Departments of Physiology and Developmental Biology, University of Texas Southwestern Medical Center, Dallas, 75390, USA.
authors.forename: XunLei
authors.initials: X
authors.lastname: Kang
authors.affiliation: Departments of Physiology and Developmental Biology, University of Texas Southwestern Medical Center, Dallas, 75390, USA.
authors.forename: Mi
authors.initials: M
authors.lastname: Deng
authors.affiliation: Departments of Physiology and Developmental Biology, University of Texas Southwestern Medical Center, Dallas, 75390, USA.
authors.forename: ZhiGang
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Departments of Physiology and Developmental Biology, University of Texas Southwestern Medical Center, Dallas, 75390, USA.
authors.forename: Jaehyup
authors.initials: J
authors.lastname: Kim
authors.affiliation: Departments of Physiology and Developmental Biology, University of Texas Southwestern Medical Center, Dallas, 75390, USA. Alec.Zhang@UTSouthwestern.edu.
authors.forename: ChengCheng
authors.initials: C
authors.lastname: Zhang
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D020033:Protein Isoforms; D011971:Receptors, Immunologic; D054558:Protein Tyrosine Phosphatases, Non-Receptor
keywords: CD85; HLA; ILT; ITAM; ITIM; LILRB; LIR; MHC; SHIP; SHP-1; SHP-2; cancer; immunoglobulin-like transcript; immunoreceptor tyrosine-based activation motif; immunoreceptor tyrosine-based inhibitory motifs; leukemia; leukocyte immunoglobulin-like receptor; leukocyte immunoglobulin-like receptor subfamily B; phosphatase; signal transduction