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It covers LILRB4 effects on T cells, dendritic cells, NK cells, and macrophages, including dual roles in immune activation and suppression. 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\nLeukocyte immunoglobulin‐like receptor B4: A keystone in immune modulation and therapeutic target in cancer and beyond  \nQi Liu1,2  | Yuyang Liu3 | Zhanyu Yang1  \n1Faculty of Hepato‐Pancreato‐Biliary Surgery, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing, China 2Medical School of Chinese People's Liberation Army, Beijing, China 3Department of Neurosurgery, 920th Hospital of Joint Logistics Support Force, Kunming, Yunnan, China  \nCorrespondence  \nZhanyu Yang, Faculty of Hepato‐ Pancreato‐Biliary Surgery, The First Medical Center, Chinese People's Liberation Army General Hospital, No.28 Fuxing Rd, Haidian District, Beijing 100853, China.  \nEmail: [zhanyuyang@163.com](zhanyuyang@163.com)  \nFunding information None  \nAbstract  \nLeukocyte immunoglobulin‐like receptor B4 (LILRB4) significantly impacts immune regulation and the pathogenesis and progression of various cancers. This review discusses LILRB4's structural attributes, expression patterns in immune cells, and molecular mechanisms in modulating immune responses. We describe the influence of LILRB4 on T cells, dendritic cells, NK cells, and macrophages, and its dual role in stimulating and suppressing immune activities. The review discusses the current research on LILRB4's involvement in acute myeloid leukemia, chronic lymphocytic leukemia, and solid tumors, such as colorectal cancer, pancreatic cancer, non‐small cell lung cancer, hepatocellular carcinoma, and extramedullary multiple myeloma. The review also describes LILRB4's role in autoimmune disorders, infectious diseases, and other conditions. We evaluate the recent advancements in targeting LILRB4 using monoclonal antibodies and peptide inhibitors and their therapeutic potential in cancer treatment. Together, these studies underscore the need for  \nAbbreviations: AD, alzheimer's disease; AG490, JAK2 inhibitor; ALI, acute lung injury; AML, acute myeloid leukemia; ApoE, apolipoprotein E; ARG1, arginase‐1; Aβ, amyloid‐β; CAR‐T cells, chimeric antigen receptor T cells; CD166, cluster of differentiation 166; CD85k, cluster of differentiation 85k; CLL, chronic lymphocytic leukemia; COPD, chronic obstructive pulmonary disease; COVID‐19, coronavirus disease 2019; CTGF, connective tissue growth factor; DEGs, differentially expressed genes; DFS, disease‐free survival; ECM, extracellular matrix; FN, fibronectin; HASMCs, human aortic smooth muscle cells; HCC, hepatocellular carcinoma; HIV, human immunodeficiency virus; HLA‐G, human leukocyte antigen G; IBD, inflammatory bowel disease; IL, interleukin; ILT3, immunoglobulin‐like transcript 3; ILT3‐Fc, immunoglobulin‐like transcript 3 ‐ Fc; IM, intrapulmonary metastasis; ITIMs, immunoreceptor tyrosine‐based inhibitory motifs; JAK2, janus kinase 2; KD, kawasaki disease; LILRB4, leukocyte immunoglobulin‐like receptor B4; LILRs, leukocyte immunoglobulin‐like receptors; LIR5, leukocyte immunoglobulin‐like receptor 5; mAb, monoclonal antibody; MD, molecular dynamics; MDSCs, myeloid‐derived suppressor cells; MMP2, matrix metalloproteinase 2; MPLC, multiple primary lung cancers; NAFLD, nonalcoholic fatty liver disease; NFκB, nuclear factor kappa B; NK cells, natural killer cells; NSCLC, non‐small cell lung cancer; PCH, pathological cardiac hypertrophy; PIR‐B, paired immunoglobulin‐like type 2 receptor beta; RELT, receptor expressed in lymphoid tissues; SHP‐1, src homology 2 domain‐containing protein tyrosine phosphatase 1; SHP‐2, src homology 2 domain‐containing protein tyrosine phosphatase 2; SLE, systemic lupus erythematosus; SM22α, smooth muscle 22 alpha; STAT3, signal transducer and activator of transcription 3; STAT6, signal transducer and activator of transcription 6; T cells, effector T cells; TAMs, tumor‐associated macrophages; Th cells, T helper cells; TME, tumor microenvironment; uPAR, Urokinase‐type plasminogen activator receptor; α‐SMA, alpha‐smooth muscle actin;αVβ3, integrin alpha V beta3 .  \nQi Liu and Y","cbCaihepsx2rxVIf","https://ap.wps.com/l/cbCaihepsx2rxVIf","pdf",1201055,13,"English","# Introduction\n## LILRB4 as an immune inhibitory receptor and regulator of tolerance\n## Rationale for targeting LILRB4 in oncology\n# Therapeutic targeting approaches","[{\"question\":\"What role does LILRB4 play in immune regulation?\",\"answer\":\"LILRB4 functions as a myeloid inhibitory receptor involved in regulating immune tolerance and immune responses.\"},{\"question\":\"Which immune cells are discussed in relation to LILRB4 function?\",\"answer\":\"The review describes impacts of LILRB4 on T cells, dendritic cells, NK cells, and macrophages.\"},{\"question\":\"How is LILRB4 being targeted therapeutically?\",\"answer\":\"Recent advances focus on targeting LILRB4 using monoclonal antibodies and peptide inhibitors, aiming to exploit its therapeutic potential in cancer.\"}]","Leukocyte Immunoglobulin-like Receptor B4 - A Keystone in Immune Modulation and Therapeutic Target in Cancer and Beyond | PDF",1789998983,33]