Perspectives of targeting LILRB1 in innate and adaptive immune checkpoint therapy of cancer

Abstract

Immune checkpoint blockade is a compelling approach in tumor immunotherapy. Blocking inhibitory pathways in T cells has demonstrated clinical efficacy in different types of cancer and may hold potential to also stimulate innate immune responses. A novel emerging potential target for immune checkpoint therapy is leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1). LILRB1 belongs to the superfamily of leukocyte immunoglobulin-like receptors and exerts inhibitory functions. The receptor is expressed by a variety of immune cells including macrophages as well as certain cytotoxic lymphocytes and contributes to the regulation of different immune responses by interaction with classical as well as non-classical human leukocyte antigen (HLA) class I molecules. LILRB1 has gained increasing attention as it has been demonstrated to function as a phagocytosis checkpoint on macrophages by recognizing HLA class I, which represents a ‘Don’t Eat Me!’ signal that impairs phagocytic uptake of cancer cells, similar to CD47. The specific blockade of the HLA class I:LILRB1 axis may provide an option to promote phagocytosis by macrophages and also to enhance cytotoxic functions of T cells and natural killer (NK) cells. Currently, LILRB1 specific antibodies are in different stages of pre-clinical and clinical development. In this review, we introduce LILRB1 and highlight the features that make this immune checkpoint a promising target for cancer immunotherapy.

SorLA restricts TNFα release from microglia to shape a glioma-supportive brain microenvironment

“…2C ). These interactions may be associated with enhanced tissue infiltration (Schenkel et al, 2004 ; Pham et al, 2012 ) and induction of immunosuppressive GAMs phenotype (Zeller et al, 2023 ), respectively. In turn, high- SORL1 GAMs sent pro-tumorigenic signals to the tumor cells (Fig.…”

NK Cell–Monocyte Cross-talk Underlies NK Cell Activation in Severe COVID-19

“…Our use of the recently developed computational technique Scriabin to infer cell–cell communication between NK cells and other peripheral immune cells at the single-cell level also provided candidate contact-dependent interactions that may underlie the activation and dysfunction of CD56 dim NK cells by monocytes in severe COVID-19. Notably, many of the interactions predicted by Scriabin to be upregulated in severe COVID-19 are interactions between class I MHC molecules and KIR or LILRB family receptors, which typically have an inhibitory effect on NK cell cytotoxicity ( 85 , 86 ). The activating and inhibitory signals received by CD56 dim NK cells from monocytes in severe COVID-19 may therefore explain these cells’ activated yet dysfunctional state.…”

Critical gene signature and immunological characterization in peripheral vascular atherosclerosis: novel insights from mendelian randomization and transcriptomics

“…Its functions encompass immune cell differentiation, proliferation, and cytokine release. It is a potential target for immune checkpoint therapy ( Zeller et al, 2023 ). PLAU codes for plasminogen activator, urokinase, which is a secreted serine protease involved in fibrinolysis.…”

“…The positive correlations of ARHGAP25, HVCN1, LILRB1, and RBM47 with memory B cells indicate potential roles of these genes in regulating memory B cell function. LILRB1, for example, has been previously implicated in B cell regulation, where the antibody-mediated crosslinking of LILRB1 has been shown to disrupt B cell receptor activation, leading to diminished Ca2+ mobilization ( Colonna et al, 1997 ; Zeller et al, 2023 ). On the other hand, CFL2’s negative correlation with memory B cells suggests a potential inhibitory role in memory B cell development or function.…”