Inhibitory leukocyte immunoglobulin-like receptors: Immune checkpoint proteins and tumor sustaining factors

Xunlei Kang, Jaehyup Kim, Mi Deng Ph.D., Samuel John, Heyu Chen, Guojin Wu, Hiep Phan, Chengcheng Zhang

Research output: Contribution to journalReview articlepeer-review

122 Scopus citations


Inhibitory leukocyte immunoglobulin-like receptors (LILRBs 1-5) transduce signals via intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that recruit protein tyrosine phosphatase nonreceptor type 6 (PTPN6 or SHP-1), protein tyrosine phosphatase non-receptor type 11 (PTPN11 or SHP-2), or Src homology 2 domain-containing inositol phosphatase (SHIP), leading to negative regulation of immune cell activation. Certain of these receptors also play regulatory roles in neuronal activity and osteoclast development. The activation of LILRBs on immune cells by their ligands may contribute to immune evasion by tumors. Recent studies found that several members of LILRB family are expressed by tumor cells, notably hematopoietic cancer cells, and may directly regulate cancer development and relapse as well as the activity of cancer stem cells. LILRBs thus have dual concordant roles in tumor biology - as immune checkpoint molecules and as tumor-sustaining factors. Importantly, the study of knockout mice indicated that LILRBs do not affect hematopoiesis and normal development. Therefore LILRBs may represent ideal targets for tumor treatment. This review aims to summarize current knowledge on expression patterns, ligands, signaling, and functions of LILRB family members in the context of cancer development.

Original languageEnglish (US)
Pages (from-to)25-40
Number of pages16
JournalCell Cycle
Issue number1
StatePublished - Jan 1 2016


  • CD85
  • Cancer
  • HLA
  • ILT
  • ITAM
  • ITIM
  • Immunoglobulin-like transcript
  • Immunoreceptor tyrosine-based activation motif
  • Immunoreceptor tyrosine-based inhibitory motifs
  • LIR
  • Leukemia
  • Leukocyte immunoglobulinlike receptor
  • Leukocyte immunoglobulinlike receptor subfamily B
  • MHC
  • Phosphatase
  • SHIP
  • SHP-1
  • SHP-2
  • Signal transduction

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology


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