Targeting Siglec-E facilitates tumor vaccine-induced antitumor immunity in renal carcinoma DOI Creative Commons
Yanyan Zheng, Jiawei Wang,

Guangya Zhao

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(1), P. e010521 - e010521

Published: Jan. 1, 2025

Siglec-E is an immune checkpoint inhibitory molecule. Expression of on the cells has been shown to promote tumor regression. This study aimed develop adenovirus (Ad) vaccine targeting and carbonic anhydrase IX (CAIX) (Ad-Siglec-E/CAIX) evaluate its potential antitumor effects in several preclinical renal cancer models. Ad vaccines encoding or CAIX were developed evaluated for their therapeutic mouse subcutaneous, lung metastatic, orthotopic The expression Ad-Siglec-E/CAIX was confirmed via PCR flow cytometry. Immune responses induced by assessed vitro vivo using cytometry, immunohistochemistry, ELISA, histological analysis, cell proliferation, enzyme-linked immunosorbent spot, cytotoxic T lymphocytes (CTL) killing, depletion assays. increase tumor-infiltrated cells, significantly suppressed subcutaneous growth carcinoma. Immunization with promoted induction maturation CD11c+ dendritic subsets, which turn enhanced tumor-specific CD8+ responses, as evidenced increased proliferation CTL activity. Importantly, deletion abolished effect vaccine, highlighting essential role functional responses. potent efficacy also observed metastasis models through Our results indicate that enhances Ad-CAIX against carcinoma, providing a promising option solid tumors.

Language: Английский

Antitumor efficacy and potential mechanism of FAP-targeted radioligand therapy combined with immune checkpoint blockade DOI Creative Commons
Liang Zhao, Yizhen Pang, Yangfan Zhou

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: June 2, 2024

Radiotherapy combined with immune checkpoint blockade holds great promise for synergistic antitumor efficacy. Targeted radionuclide therapy delivers radiation directly to tumor sites. LNC1004 is a fibroblast activation protein (FAP)-targeting radiopharmaceutical, conjugated the albumin binder Evans Blue, which has demonstrated enhanced uptake and retention in previous preclinical clinical studies. Herein, we demonstrate that

Language: Английский

Citations

15
Dissecting the Ability of Siglecs To Antagonize Fcγ Receptors DOI Creative Commons
Kelli A. McCord, Chao Wang,

Mirjam Anhalt

et al.

ACS Central Science, Journal Year: 2024, Volume and Issue: 10(2), P. 315 - 330

Published: Jan. 17, 2024

Fcγ receptors (FcγRs) play key roles in the effector function of IgG, but their inappropriate activation plays a role several disease etiologies. Therefore, it is critical to better understand how FcγRs are regulated. Numerous studies suggest that sialic acid-binding immunoglobulin-type lectins (Siglecs), family immunomodulatory receptors, modulate FcγR activity; however, unclear circumstances which Siglecs can antagonize and have this ability. Using liposomes displaying selective ligands coengage with specific Siglec, we explore ability Siglec-3, Siglec-5, Siglec-7, Siglec-9 signaling downstream FcγRs. We demonstrate Siglec-3 fully inhibit U937 cells when coengaged Cells expressing Siglec mutants reveal differential for tyrosine-based inhibitory motif (ITIM) switch (ITSM) inhibition. Imaging flow cytometry enabled visualization SHP-1 recruitment an ITIM-dependent manner, while SHP-2 more ITSM-dependent. Conversely, both cytosolic motifs contribute SHP-1/2 recruitment. Siglec-7 poorly antagonizes two reasons: masking by cis differences its ITIM ITSM. A chimera extracellular domains Siglec-5 tail strongly inhibits coengaged, providing evidence like Additionally, inhibited These results mediating inhibition context immunological synapse, has important relevance effectiveness immunotherapies.

Language: Английский

Citations

13
Engagement of sialylated glycans with Siglec receptors on suppressive myeloid cells inhibits anticancer immunity via CCL2 DOI Creative Commons

Ronja Wieboldt,

Michael T. Sandholzer, Emanuele Carlini

et al.

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(5), P. 495 - 509

Published: March 6, 2024

Abstract The overexpression of sialic acids on glycans, called hypersialylation, is a common alteration found in cancer cells. Sialylated glycans can enhance immune evasion by interacting with acid-binding immunoglobulin-like lectin (Siglec) receptors tumor-infiltrating Here, we investigated the effect sialylated and their interaction Siglec myeloid-derived suppressor cells (MDSCs). We that MDSCs derived from blood lung patients tumor-bearing mice strongly express inhibitory are highly sialylated. In murine models emergency myelopoiesis, Siglec-E knockout myeloid resulted prolonged survival increased tumor infiltration activated T Targeting suppressive blocking or desialylation reduced potential. further identified CCL2 as mediator involved T-cell suppression upon between sialoglycans MDSCs. Our results demonstrated inhibit anticancer immunity modulating expression.

Language: Английский

Citations

12
Lactate reprograms glioblastoma immunity through CBX3-regulated histone lactylation DOI Creative Commons
Shuai Wang, Tengfei Huang, Qiulian Wu

et al.

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(22)

Published: Nov. 14, 2024

Glioblastoma (GBM), an aggressive brain malignancy with a cellular hierarchy dominated by GBM stem cells (GSCs), evades antitumor immunity through mechanisms that remain incompletely understood. Like most cancers, GBMs undergo metabolic reprogramming toward glycolysis to generate lactate. Here, we show lactate production patient-derived GSCs and microglia/macrophages induces tumor cell epigenetic histone lactylation, activating modification leads immunosuppressive transcriptional programs suppression of phagocytosis via upregulation CD47, "don't eat me" signal, in cells. Leveraging these findings, pharmacologic targeting augments efficacy anti-CD47 therapy. Mechanistically, lactylated interacts the heterochromatin component chromobox protein homolog 3 (CBX3). Although CBX3 does not possess direct lactyltransferase activity, binds acetyltransferase (HAT) EP300 induce increased substrate specificity lactyl-CoA shift cytokine profile. Targeting inhibits growth both cell–intrinsic phagocytosis. Collectively, results suggest mediates metabolism-induced contributes CD47-dependent immune evasion, which can be leveraged augment immuno-oncology therapies.

Language: Английский

Citations

11
Sialic acid metabolism-based classification reveals novel metabolic subtypes with distinct characteristics of tumor microenvironment and clinical outcomes in gastric cancer DOI Creative Commons

Junjie Jiang,

Yiran Chen, Yangyang Zheng

et al.

Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)

Published: Feb. 22, 2025

High heterogeneity in gastric cancer (GC) remains a challenge for standard treatments and prognosis prediction. Dysregulation of sialic acid metabolism (SiaM) is recognized as key metabolic hallmark tumor immune evasion metastasis. Herein, we aimed to develop SiaM-based classification GC. SiaM-related genes were obtained from the MsigDB database. Bulk single-cell transcriptional data 956 GC patients acquired GEO, TCGA, MEDLINE databases. Proteomic profiles 20 samples derived our institution. The consensus clustering algorithm was applied identify clusters. model established via LASSO regression evaluated Kaplan‒Meier curve ROC analyses. In vitro vivo experiments conducted explore function ST3GAL1 Three SiaM clusters presented distinct patterns clinicopathological features, transcriptomic alterations, microenvironment landscapes Compared with A B, cluster C elevated activity, higher metastatic potential, more abundant immunosuppressive worse prognosis. Based on differentially expressed between these clusters, risk six (ARHGAP6, ST3GAL1, ADAM28, C7, PLCL1, TTC28) then constructed. exhibited robust performance predicting peritoneal metastasis four independent cohorts. As hub gene model, promoted cell migration invasion vivo. Our study proposed novel that identified three subtypes characteristics clinical outcomes

Language: Английский

Citations

1
Implantable Microneedle‐Mediated Eradication of Postoperative Tumor Foci Mitigates Glioblastoma Relapse DOI Open Access
Yulin Zhang, Z Fang,

Zejuan Liu

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 29, 2024

Abstract Glioblastoma multiforme (GBM) remains incurable despite multimodal treatments after surgical debulking. Almost all patients with GBM relapse within a narrow margin (2–3 cm) of the initial resected lesion due to unreachable residual cancerous cells. Here, completely biodegradable microneedle for cavity delivery glioblastoma‐associated macrophages (GAMs)‐activating immune nano‐stimulator that mitigates glioblastoma is reported. The tumor lesion‐directed biocompatible releases and toll‐like receptor 9 agonist in controlled manner until microneedles degrade over 1 week, efferently induce situ phonotypic shifting GAMs from anti‐ pro‐inflammatory recurrence obviously inhibited. implantable offer significant improvement conventional transdermal ones, as they are 100% degradable, ensuring safe application cavities. It also revealed T cells recruited niche initiate anti‐tumor response eradicate Taken together, this work provides potential strategy immunomodulating postoperative mitigate patients, which may have broad applications other malignancies intervention.

Language: Английский

Citations

8
Bacterial Biohybrids for Invasion of Tumor Cells Promote Antigen Cross‐Presentation Through Gap Junction DOI
Wen Li, Qi‐Wen Chen, Jin‐Xuan Fan

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(25)

Published: April 2, 2024

Due to inherent differences in cellular composition and metabolic behavior with host cells, tumor-harbored bacteria can discriminatorily affect tumor immune landscape. However, the mechanisms by which intracellular antigen presentation process between cells antigen-presenting (APCs) are largely unknown. The invasion of attenuated Salmonella VNP20009 (VNP) into is investigated an attempt made modulate this modifying positively charged polymers on surface VNP. It found that non-toxic chitosan oligosaccharide (COS) modified VNP (VNP@COS) bolsters formation gap junction APCs enhancing ability infect cells. On basis, a bacterial biohybrid designed promote situ cross-presentation through induced junction. This also enhances expression major histocompatibility complex class I molecules incorporation Mdivi-1 coupled VNP@COS. strategic integration serves heighten immunogenic exposure antigens; while, preserving cytotoxic potency T A strategy proposed precisely controlling function local effects microorganisms within tumors.

Language: Английский

Citations

6
From mechanism to therapy: the journey of CD24 in cancer DOI Creative Commons
Kai Zhao,

Caifeng Wu,

Xiangjun Li

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: May 31, 2024

CD24 is a glycosylphosphatidylinositol-anchored protein that expressed in wide range of tissues and cell types. It involved variety physiological pathological processes, including adhesion, migration, differentiation, apoptosis. Additionally, has been studied extensively the context cancer, where it found to play role tumor growth, invasion, metastasis. In recent years, there growing interest as potential therapeutic target for cancer treatment. This review summarizes current knowledge CD24, its structure, function, cancer. Finally, we provide insights into clinical application discuss possible approaches development targeted therapies.

Language: Английский

Citations

6
Brain macrophage senescence in glioma DOI
Lu Li, Tianhe Zhang,

Meiling Xiao

et al.

Seminars in Cancer Biology, Journal Year: 2024, Volume and Issue: 104-105, P. 46 - 60

Published: Aug. 3, 2024

Language: Английский

Citations

6
Therapeutic potential to target sialylation and SIGLECs in neurodegenerative and psychiatric diseases DOI Creative Commons
Jannis Wißfeld,

Tawfik Abou Assale,

Germán Cuevas-Ríos

et al.

Frontiers in Neurology, Journal Year: 2024, Volume and Issue: 15

Published: March 11, 2024

Sialic acids, commonly found as the terminal carbohydrate on glycocalyx of mammalian cells, are pivotal checkpoint inhibitors innate immune system, particularly within central nervous system (CNS). acid-binding immunoglobulin-like lectins (SIGLECs) expressed microglia key players in maintaining microglial homeostasis by recognizing intact sialylation. The finely balanced sialic acid-SIGLEC ensures prevention excessive and detrimental responses CNS. However, loss sialylation SIGLEC receptor dysfunctions contribute to several chronic CNS diseases. Genetic variants SIGLEC3 / CD33 , SIGLEC11 SIGLEC14 have been associated with neurodegenerative diseases such Alzheimer’s disease, while sialyltransferase ST8SIA2 SIGLEC4 MAG linked psychiatric schizophrenia, bipolar disorders, autism spectrum disorders. Consequently, immune-modulatory functions polysialic acids binding antibodies exploited experimentally animal models disease inflammation-induced tissue damage, including retinal damage. While potential these therapeutic approaches is evident, only a few therapies target either or receptors tested patient clinical trials. Here, we provide an overview critical role played axis shaping activation function context neurodegeneration synaptopathies discuss current landscape that SIGLECs.

Language: Английский

Citations

5