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 language | English (US) |
|---|---|
| Pages (from-to) | 1216-1225 |
| Number of pages | 10 |
| Journal | Science China Life Sciences |
| Volume | 58 |
| Issue number | 12 |
| DOIs | |
| State | Published - 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)
Cite this
Inhibitory leukocyte immunoglobulin-like receptors in cancer development. / Zhang, FeiFei F.; Zheng, JunKe K.; Kang, XunLei L.; Deng Ph.D., Mi; Lu, Zhigang; Kim, Jaehyup; Zhang, Chengcheng.
In: Science China Life Sciences, Vol. 58, No. 12, 01.12.2015, p. 1216-1225.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibitory leukocyte immunoglobulin-like receptors in cancer development
AU - Zhang, FeiFei F.
AU - Zheng, JunKe K.
AU - Kang, XunLei L.
AU - Deng Ph.D., Mi
AU - Lu, Zhigang
AU - Kim, Jaehyup
AU - Zhang, Chengcheng
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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.
AB - 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.
KW - cancer
KW - CD85
KW - HLA
KW - ILT
KW - immunoglobulin-like transcript
KW - immunoreceptor tyrosine-based activation motif
KW - immunoreceptor tyrosine-based inhibitory motifs
KW - ITAM
KW - ITIM
KW - leukemia
KW - leukocyte immunoglobulin-like receptor
KW - leukocyte immunoglobulin-like receptor subfamily B
KW - LILRB
KW - LIR
KW - MHC
KW - phosphatase
KW - SHIP
KW - SHP-1
KW - SHP-2
KW - signal transduction
UR - http://www.scopus.com/inward/record.url?scp=84949321480&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84949321480&partnerID=8YFLogxK
U2 - 10.1007/s11427-015-4925-1
DO - 10.1007/s11427-015-4925-1
M3 - Article
C2 - 26566804
AN - SCOPUS:84949321480
VL - 58
SP - 1216
EP - 1225
JO - Science China. Life sciences
JF - Science China. Life sciences
SN - 1674-7305
IS - 12
ER -