摘要
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.
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.
基金
supported b y the Na tional In stitu te o f Health(1R01CA172268)
the Leukemia&Lymphoma Society(1024-14
TRP-6024-14)
the Robert A.Welch Foundation(I-1834)
the Cancer Prevention and Research Institute of Texas(RP140402 and DP150056)
the Innovation Program of Shanghai Municipal Education Commission(13G20)
the Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning
the National Natural Science Foundation of China(81370654
81422001
81471524)
