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Inhibitory leukocyte immunoglobulin-like receptors in cancer development

Science China(Life Sciences) 2015年第12期58卷 1216-1225页

作者： ZHANG FeiFei ZHENG JunKe KANG XunLei DENG Mi LU ZhiGang KIM Jaehyup ZHANG ChengCheng Hongqiao International Institute of Medicine Shanghai Tongren Hospital Faculty of Basic Medicine Shanghai Jiao Tong University School of Medicine Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education Shanghai Jiao Tong University School of Medicine Departments of Physiology and Developmental Biology University of Texas Southwestern Medical Center

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.

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

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Co-Inhibitors of Second Signal of Lymphocyte Response in Human Renal Transplants: PD-L2, GITR, and ILT-2/3/5 Positive Cells from Aspiration Biopsies Associate with Acute Rejection-Freedom

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Open Journal of Nephrology 2021年第1期11卷 58-77页

作者： Paula D. P. Xavier José Gerardo G. Oliveira Instituto Português do Sangue e da Transplantaç ã o área Transplanta&#231 ã o Rua do Bolama Porto Portugal GCCT Centro Hospitalar Universitário S. Jo&#227 o Alameda Hernani Monteiro Porto Portugal CINTESIS Faculdade de Medicina da Universidade do Porto Alameda Hernani Monteiro Porto Portugal

Following organ transplantation, the outcome of the encounter between an APC and a T lymphocyte is strongly dependent on the presence of costimulatory and co-inhibitory molecules, the former associated with allograft rejection and the latter with allograft acceptance. We evaluated the expression of PD-L2, GITR, ILT-2/3/5, and ILT-4 on graft-infiltrating cells procured by Fnab from human KTx under different immunosuppressive regimens. Methods: Fnab biopsies were performed on days 7 or 14 - 30 in stable KTx and on the day of acute rejection diagnosis. Cytopreparations were studied by the enzymatic avidin biotin complex staining. Results: Acute rejection group showed a significant down-regulated expression of PD-L2, GITR, and ILT-2/3/5 as compared to stable group, while for ILT-4 we did not find significant difference. Anti-IL2αR and rapamicyn treatment trend to down-regulate ILT-4 expression, although meaningless. A significantly positive correlation was observed between PD-L2 and GITR expression in Fnab. The PPV for acute rejection diagnosis for both PD-L2 and GITR was clearly above 0.8. Conclusions: Our findings point to an early entrance of cells expressing PD-L2, GITR and ILT-2/3/5 inside human KTx who are going to remain rejection-free. Both PD-L2 and GITR shared a high ability to rule-in and rule-out acute rejection.

关键词： Antigen-Presenting Cell Fine-Needle Aspiration Biopsy Glucocorticoid-Induced Tumor Necrosis Factor Receptor immunoglobulin-like transcript Kidney Transplant Programmed Death-Ligand 2

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