Deng Mi, Chen Heyu, Liu Xiaoye, Huang Ryan, He Yubo, Yoo Byounggyu, Xie Jingjing, John Samuel, Zhang Ningyan, An Zhiqiang, Zhang Cheng Cheng
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Department of Pediatrics, Pediatric Hematology-Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Antib Ther. 2021 Feb 9;4(1):16-33. doi: 10.1093/abt/tbab002. eCollection 2021 Jan.
Inhibitory leukocyte immunoglobulin-like receptors (LILRBs 1-5) transduce signals via intracellular immunoreceptor tyrosine-based inhibitory motifs that recruit phosphatases to negatively regulate immune activation. The activation of LILRB signaling in immune cells may contribute to immune evasion. In addition, the expression and signaling of LILRBs in cancer cells especially in certain hematologic malignant cells directly support cancer development. Certain LILRBs thus have dual roles in cancer biology-as immune checkpoint molecules and tumor-supporting factors. Here, we review the expression, ligands, signaling, and functions of LILRBs, as well as therapeutic development targeting them. LILRBs may represent attractive targets for cancer treatment, and antagonizing LILRB signaling may prove to be effective anti-cancer strategies.
抑制性白细胞免疫球蛋白样受体(LILRBs 1-5)通过细胞内基于免疫受体酪氨酸的抑制基序转导信号,这些基序招募磷酸酶以负向调节免疫激活。免疫细胞中LILRB信号的激活可能有助于免疫逃逸。此外,LILRBs在癌细胞尤其是某些血液系统恶性细胞中的表达和信号传导直接支持癌症发展。因此,某些LILRBs在癌症生物学中具有双重作用——作为免疫检查点分子和肿瘤支持因子。在此,我们综述LILRBs的表达、配体、信号传导和功能,以及针对它们的治疗进展。LILRBs可能是有吸引力的癌症治疗靶点,拮抗LILRB信号传导可能被证明是有效的抗癌策略。