Lectin Galactoside-binding Soluble 3 Binding Protein (LGALS3BP) Is a Tumor-associated Immunomodulatory Ligand for CD33-related Siglecs

Abstract

Background: Engagement of inhibitory CD33-related Siglecs on immune cells has been shown to influence interactions with cancer cells, including tumor immune evasion. Results:LGALS3BP binds with high affinity to CD33-related Siglecs and inhibits neutrophil activation. Conclusion: We identify LGALS3BP as novel, cancer-associated Siglec ligand that can influence neutrophil activation. Significance: The engagement of inhibitory CD33-related Siglecs by LGALS3BP could support immune evasion of tumor cells.

Self-associated molecular patterns mediate cancer immune evasion by engaging Siglecs on T cells

“…+ TILs from NSCLC samples activated with anti-CD3/anti-CD28 antibodies expressed significantly higher surface levels of CD25 ( Figure 3A), CD69 ( Figure 3B), and the newly identified activation marker Siglec-5 (Supplemental Figure 4C) compared with similarly actiby engaging inhibitory CD33rSiglecs, such as Siglec-7 and Siglec-9 (21)(22)(23)(24)(25)(26). Engagement of Siglec-7 and Siglec-9 inhibits NK cellmediated tumor cell killing in vitro (22,23).…”

“…Engagement of Siglec-7 and Siglec-9 inhibits NK cellmediated tumor cell killing in vitro (22,23). Siglec-9 and its murine functional paralog Siglec-E have also been implicated in myeloid cell-mediated cancer progression (21,24). Binding of the cancerassociated sialylated glycoform of MUC1 to Siglec-9 on macrophages can induce a tumor-associated macrophage (TAM) phenotype that can promote cancer progression and immune evasion (25).…”

“…Next, we wanted to explore the functional implication of Siglec expression on T cells. We used the high-affinity CD33rSiglec ligand LGALS3BP, which is upregulated in NSCLC (24). LGALS3BP inhibited CD8 + T cell activation in a sialic aciddependent fashion ( Figure 4A, Supplemental Figure 7, A and B).…”

Targeting Neutrophils in Severe Asthma via Siglec-9

“…Although further verification is needed, the potential interaction of Siglec-9 expressed on NK cells and myelomonocytic cells with sialylated tumorassociated ligands on tumor cells may play a role in cancer progression. A novel sialylated ligand of Siglec-9-Nglycosylated lectin galactoside-binding soluble 3 binding protein (LGALS3BP) was identified from tumor cell extracts by means of affinity chromatography [71].…”

A Proteomic Analysis of the Malignant Mesothelioma Secretome Using iTRAQ

“…This positive association with survival may be due to inhibition of WNT signalling as has been demonstrated in colorectal cancer (41,42). LGALS3BP may inhibit immune responses to cancer (43).…”