Inhibitory leukocyte immunoglobulin-like receptors in cancer development

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...

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Bibliographic Details
Published in:	Science China. Life Sciences 2015-12, Vol.58 (12), p.1216-1225
Main Authors:	Zhang, FeiFei, Zheng, JunKe, Kang, XunLei, Deng, Mi, Lu, ZhiGang, Kim, Jaehyup, Zhang, ChengCheng
Format:	Article
Language:	eng
Subjects:	Amino Acid Motifs Amino Acid Sequence Antigens, CD - metabolism Biomedical and Life Sciences Humans Life Sciences Models, Biological Neoplasms - metabolism Neoplasms - pathology Protein Binding Protein Isoforms - metabolism Protein Tyrosine Phosphatases, Non-Receptor - metabolism Receptors, Immunologic - metabolism Review 信号转导免疫球蛋白免疫细胞受体表达白细胞肿瘤细胞蛋白酪氨酸磷酸酶调节作用
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Summary:	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.
ISSN:	1674-7305 1869-1889