Inhibitory leukocyte immunoglobulin-like receptors in cancer development

FeiFei F. Zhang, JunKe K. Zheng, XunLei L. Kang, Mi Deng Ph.D., Zhigang Lu, Jaehyup Kim, Chengcheng Zhang

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1216-1225
Number of pages10
JournalScience China Life Sciences
Volume58
Issue number12
DOIs
StatePublished - Dec 1 2015

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Keywords

  • cancer
  • CD85
  • HLA
  • ILT
  • immunoglobulin-like transcript
  • immunoreceptor tyrosine-based activation motif
  • immunoreceptor tyrosine-based inhibitory motifs
  • ITAM
  • ITIM
  • leukemia
  • leukocyte immunoglobulin-like receptor
  • leukocyte immunoglobulin-like receptor subfamily B
  • LILRB
  • LIR
  • MHC
  • phosphatase
  • SHIP
  • SHP-1
  • SHP-2
  • signal transduction

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Environmental Science(all)

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