Ask about this productRelated genes to: SIGLEC7 Blocking Peptide
- Gene:
- SIGLEC7 NIH gene
- Name:
- sialic acid binding Ig like lectin 7
- Previous symbol:
- SIGLEC19P, SIGLECP2
- Synonyms:
- SIGLEC-7, p75/AIRM1, QA79, CD328
- Chromosome:
- 19q13.41
- Locus Type:
- gene with protein product
- Date approved:
- 2000-01-26
- Date modifiied:
- 2016-01-20
Related products to: SIGLEC7 Blocking Peptide
Related articles to: SIGLEC7 Blocking Peptide
- Immune evasion is one of the critical factors contributing to the advanced progression of colorectal cancer (CRC). Our research identified that CRC cells exhibit high expression of the zinc finger protein ZNF30, which transcriptionally activates the expression of the glycosyltransferase B4GALT2. B4GALT2 mediates the N-glycosylation of MUC20, which subsequently interacts with sialic acid-binding immunoglobulin-like lectin 7 (Siglec-7) on the surface of macrophages. This interaction induces M2 polarization of the macrophages, thereby promoting immune evasion in CRC and ultimately accelerating malignant progression. In vivo experiments also verified that the ZNF30/B4GALT2/MUC20 axis promotes the growth and metastasis of CRC. The discovery of this regulatory mechanism highlights the critical role of aberrant glycosylation of MUC20 in CRC immune evasion and offers new predictive markers and therapeutic targets for patients with advanced CRC. - Source: PubMed
Publication date: 2026/04/11
Zhi YingruZhang YifengFei HuanhuanYuan JieLiu XiaobeiLiu Wanli - Sorafenib is the first-line therapy for advanced hepatocellular carcinoma (HCC). However, acquired resistance to sorafenib remains a significant challenge. Previous studies have shown that sorafenib treatment induces the formation of truncated O-glycans in HCC cells, but the relationship between sorafenib-induced glycosylation changes and acquired therapy resistance remains unclear. Primary natural killer (NK) cells, freshly isolated from peripheral blood or following culture and expansion, expressed the glycoimmune checkpoints Siglec-7 and Siglec-9. HCC cells exhibited varying levels of Siglec-7/9 ligands on their surface. Sorafenib-resistant liver cancer cells displayed hypersialylation, leading to increased expression of surface Siglec-7/9 ligands, which conferred protection against NK cell-mediated cytotoxicity. Silencing ST3GAL1 significantly reduced Siglec-7 ligand expression on liver cancer cells, enhancing their susceptibility to NK-mediated cytotoxicity and cetuximab-induced antibody-dependent cellular cytotoxicity (ADCC) in epidermal growth factor receptor (EGFR)-expressing tumor cells. Furthermore, high ST3GAL1 expression correlated with poor clinical outcomes in patients with stage 1-2 HCC. This study highlights the critical role of ST3GAL1 in regulating Siglec-7 ligands to facilitate immune escape from NK cell cytotoxicity. Moreover, its elevated expression is associated with adverse clinical outcomes in HCC. Targeting ST3GAL1 may represent a promising strategy to enhance NK cell-mediated anti-tumor immunity in HCC. - Source: PubMed
Publication date: 2026/04/10
Fan Tan-ChiHung Tsai-HsienYeh Chau-TingLin Po-TingChang Nai-ChuanLo Tzu-ChiWu Tsai-JungYu JohnYu Alice L - Macrophages exert antitumorigenic activity through phagocytosis, but phagocytosis-enhancing therapeutics have not improved acute myeloid leukemia (AML) outcomes. To identify phagocytosis regulators, we performed CRISPR knockout screens in human AML cells cocultured with human macrophages. We found that the "don't eat me" signal CD47 inhibited mouse but not human macrophage phagocytosis. However, O-linked glycosylation and sialylation were strong negative regulators of phagocytosis. In AML, the cell surface mucin-like glycoprotein CD43 was the major effector of these pathways. Inhibition of phagocytosis by CD43 was dependent on the length of its ectodomain and independent of the macrophage sialic acid receptors SIGLEC-1, SIGLEC-7, and SIGLEC-9. The inhibitory effects of CD43 extended beyond human macrophages to natural killer and T cells. Thus, CD43 forms a glyco-immune barrier that restrains both innate and adaptive antileukemic immunity. - Source: PubMed
Publication date: 2026/04/09
Chung JoohoVallurupalli MounicaNoel SarahSchor GailMrowka SofiaScapozza IlarioDemere ZelalemKammula Sachin VHu MargaretKim Sarah YLiu YuhJongNobrega CelestePerera Jonathan JWrona EwaCheruiyot Collins KLin YunkangWu David WSaberi MariaCruickshank AidanWoods Elliot CChuong Cun LanBirocchi FilippoKammula Ashwin VAvila Omar IKnudsen NelsonKocak MustafaDoench John GProcter DeanThornton LindseyBrunner Andrew MWiner EricDeAngelo Daniel JGarcia Jacqueline SStone Richard MJenkins Russell WMaus Marcela VGraubert Timothy AYates Kathleen BGolub Todd RManguso Robert T - The glyco-immune checkpoints Siglec-7 and Siglec-9 have received considerable interest as targets for cancer immunotherapy. How Siglec-7/9-sialic acid -interactions on immune cells influence -signaling induced by tumor cells and whether Siglec-7 and -9 co-blockade can enhance immune effector cell function are key questions for clinical translation. We developed and applied single and dual Jurkat/MA NFAT-luciferase reporter cells expressing wild-type or mutant chimeric Siglec-7 and/or -9. -interactions on these Jurkat/MA reporter cells prevented Siglec-7 and -9 signaling induced by -ligands, i.e. on tumor cells. In Jurkat/MA cells expressing both receptors, Siglec-7/9 co-inhibition was essential to fully block receptor signaling. Extrapolating our findings to human primary cells, NK cell-mediated killing of melanoma and acute myeloid leukemia (AML) cell lines and patient-derived AML cells was increased upon Siglec-7 and/or -9 blockade. Importantly, co-blockade was superior to single blocking strategies and the effects were most pronounced when -ligands were removed from the NK cell' surface using sialidase. Further diving into -ligand dynamics on primary human NK cells, physiological NK cell activation with IL-2 or IFN- or IL-15/IL-2-induced proliferation was shown to significantly downregulate Siglec-7 and -9 -ligand expression. Moreover, Siglec-7 and -9 ligands were progressively downregulated with each round of NK cell division. Taken together, our findings highlight the important role of -interactions in regulating -interactions and emphasize the potential of simultaneously blocking Siglec-7 and -9 for clinical applications. These insights may guide the design of next-generation Siglec-targeted immunotherapies. - Source: PubMed
Publication date: 2026/04/02
van Eck van der Sluijs JesperValk Anne H Cvan Houtum Eline J HKers-Rebel Esther DLooman MaaikeHobo WillemijnMarneth Anna EDolstra Harryvan den Boogaard LuneBüll ChristianCornelissen Lenneke A MAdema Gosse J - Immune checkpoint receptors, including Sialic-acid-binding immunoglobulin-like lectins (Siglecs), are critical regulators of immune homeostasis. Siglecs can serve as negative regulators of Toll-like receptor (TLR) signaling, promoting the resolution of inflammatory signaling through feedback inhibition mechanisms. Previous studies demonstrated that Siglec-E, the murine homolog of the human inhibitory receptor Siglec-7, negatively regulates TLR4 signaling by controlling receptor endocytosis. This regulatory mechanism suggests that Siglec-7 may also limit TLR signaling. Here we reveal a novel mechanism whereby Siglec-7 represses endosomal TLR3 activation, compared to other TLRs, in human myeloid cells. Crosslinking Siglec-7 with antibody clone QA79 significantly reduced TNFα secretion in U937 cells, primary monocytes, and macrophages following Poly(I:C) stimulation. Mechanistically, QA79 triggers rapid FcγR-independent internalization and endolysosomal trafficking of surface Siglec-7, which enables the direct co-localization of Siglec-7 with TLR3 within the endolysosome. This co-localization between Siglec-7 and TLR3 suppresses NF-κB phosphorylation, a key pro-inflammatory signaling node downstream of TLR3. These findings establish a previously unrecognized negative regulatory role of Siglec-7 for TLR3-mediated inflammation in myeloid cells, where a disrupted interaction could contribute to autoimmune disease pathogenesis. Targeting this pathway represents a promising therapeutic approach for TLR3-driven autoimmune diseases. - Source: PubMed
Publication date: 2026/03/17
Keeney Justin NSchwarte JaninaYang BoWesseling HendrikZhang BailinMcKnight Andrew JHegde SubramanyaWang Guoxing