Sialoglycans and Siglecs Can Shape the Tumor Immune Microenvironment

Trends in Immunology, Journal Year: 2020, Volume and Issue: 41(4), P. 274 - 285

Published: March 2, 2020

Language: Английский

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Tumor microenvironment signaling and therapeutics in cancer progression

Cancer Communications, Journal Year: 2023, Volume and Issue: 43(5), P. 525 - 561

Published: April 2, 2023

Abstract Tumor development and metastasis are facilitated by the complex interactions between cancer cells their microenvironment, which comprises stromal extracellular matrix (ECM) components, among other factors. Stromal can adopt new phenotypes to promote tumor cell invasion. A deep understanding of signaling pathways involved in cell‐to‐cell cell‐to‐ECM is needed design effective intervention strategies that might interrupt these interactions. In this review, we describe microenvironment (TME) components associated therapeutics. We discuss clinical advances prevalent newly discovered TME, immune checkpoints immunosuppressive chemokines, currently used inhibitors targeting pathways. These include both intrinsic non‐autonomous TME: protein kinase C (PKC) signaling, Notch, transforming growth factor (TGF‐β) Endoplasmic Reticulum (ER) stress response, lactate Metabolic reprogramming, cyclic GMP–AMP synthase (cGAS)–stimulator interferon genes (STING) Siglec also recent Programmed Cell Death Protein 1 (PD‐1), Cytotoxic T‐Lymphocyte Associated 4 (CTLA4), T‐cell immunoglobulin mucin‐3 (TIM‐3) Lymphocyte Activating Gene 3 (LAG3) checkpoint along with C‐C chemokine receptor (CCR4)‐ class chemokines 22 (CCL22)/ 17 (CCL17), type 2 (CCR2)‐ (C‐C motif) ligand (CCL2), 5 (CCR5)‐ (CCL3) axis TME. addition, review provides a holistic TME as three‐dimensional microfluidic models believed recapitulate original characteristics patient hence may be platform study mechanisms screen for various anti‐cancer therapies. further systemic influences gut microbiota reprogramming treatment response. Overall, comprehensive analysis diverse most critical highlighting newest preclinical studies underlying biology. highlight importance technologies microfluidics lab‐on‐chip research present an overview extrinsic factors, such inhabitant human microbiome, have potential modulate biology drug responses.

Language: Английский

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Siglecs-7/9 function as inhibitory immune checkpoints in vivo and can be targeted to enhance therapeutic antitumor immunity

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(26)

Published: June 21, 2021

Significance Targeting myeloid cells represents a promising strategy to augment antitumor immunity and overcome resistance existing T cell-targeting therapies. However checkpoints that can be effectively used as immunotherapy targets are still lacking. Here, we demonstrate the therapeutic potential of targeting Siglec-7 Siglec-9 enhance in vivo. Using an immunocompetent mouse model humanized for Siglec-7/9, show these receptors inhibit endogenous immune response tissue-specific manner. These Siglecs also restrict tumor-targeting checkpoint-targeting antibodies, highlighting their significance combinatorial approaches immunotherapy. Finally, Siglec-7/9 blockade significantly reduce tumor burden vivo, supporting use antibodies therapeutically immunity.

Language: Английский

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Aberrant Sialylation in Cancer: Therapeutic Opportunities

Cancers, Journal Year: 2022, Volume and Issue: 14(17), P. 4248 - 4248

Published: Aug. 31, 2022

The surface of every eukaryotic cell is coated in a thick layer glycans that acts as key interface with the extracellular environment. Cancer cells have different ‘glycan coat’ to healthy and aberrant glycosylation universal feature cancer linked all hallmarks. This means hold huge potential for development new diagnostic therapeutic strategies. One change tumour increased sialylation, both on N-glycans O-glycans, which leads dense forest sialylated structures covering surface. hypersialylation has far-reaching consequences cells, are fundamental growth, metastasis, immune evasion drug resistance. strategies inhibit sialylation represents an important opportunity develop therapeutics. Here, I summarise recent advances target cancer, including sialyltransferase inhibitors Siglecs Selectins, discuss opportunities future.

Language: Английский

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Spatial imaging of glycoRNA in single cells with ARPLA

Nature Biotechnology, Journal Year: 2023, Volume and Issue: 42(4), P. 608 - 616

Published: May 22, 2023

Language: Английский

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Targeting the Siglec–sialic acid axis promotes antitumor immune responses in preclinical models of glioblastoma

Science Translational Medicine, Journal Year: 2023, Volume and Issue: 15(705)

Published: July 19, 2023

Glioblastoma (GBM) is the most aggressive form of primary brain tumor, for which effective therapies are urgently needed. Cancer cells capable evading clearance by phagocytes such as microglia- and monocyte-derived through engaging tolerogenic programs. Here, we found that high expression sialic acid–binding immunoglobulin-like lectin 9 (Siglec-9) correlates with reduced survival in patients GBM. Using cell-specific knockouts Siglec-E, murine functional homolog Siglec-9, together single-cell RNA sequencing, demonstrated Siglec-E inhibits phagocytosis these cells, thereby promoting immune evasion. Loss on further enhanced antigen cross-presentation production pro-inflammatory cytokines, resulted more efficient T cell priming. This bridging innate adaptive responses delayed tumor growth prolonged models Furthermore, showed combinatorial activity blockade other immunotherapies demonstrating potential targeting Siglec-9 a treatment

Language: Английский

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Mucins as multifunctional building blocks of biomaterials

Biomaterials Science, Journal Year: 2018, Volume and Issue: 6(9), P. 2282 - 2297

Published: Jan. 1, 2018

Mucins glycoproteins are emerging as a multifunctional building block for biomaterials with diverse applications in chemistry and biomedicine.

Language: Английский

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Selectins in cancer immunity

Glycobiology, Journal Year: 2017, Volume and Issue: 28(9), P. 648 - 655

Published: Dec. 18, 2017

Selectins are vascular adhesion molecules that mediate physiological responses such as inflammation, immunity and hemostasis. During cancer progression, selectins promote various steps enabling the interactions between tumor cells blood constituents, including platelets, endothelial leukocytes. carbohydrate-binding bind to sialylated, fucosylated glycan structures. The increased selectin ligand expression on correlates with enhanced metastasis poor prognosis for patients. While, many studies focused role of a mediator cell extravasation during metastasis, there is evidence activate signaling cascade regulates immune within microenvironment. L-Selectin binding induces activation leukocytes, which can be further modulated by selectin-mediated platelets cells. Selectin PSGL-1, triggers intracellular in leukocytes induced through platelet's P-selectin or E-selectin binding. In this review, I summarize selectin-induced modulation progression represents possible target controlling immunity.

Language: Английский

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Physical biology of the cancer cell glycocalyx

Nature Physics, Journal Year: 2018, Volume and Issue: 14(7), P. 658 - 669

Published: June 28, 2018

Language: Английский

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Targeting sialic acid–Siglec interactions to reverse immune suppression in cancer

Glycobiology, Journal Year: 2017, Volume and Issue: unknown

Published: Dec. 19, 2017

Changes in sialic acids cancer have been observed for many years. In particular, the increase of sialoglycan density or hypersialylation tumors has described. Recent studies identified mechanisms immune evasion based on interactions with immunoregulatory Siglec receptors that are exploited by tumor cells and microorganisms alike. Siglecs mostly inhibitory similar to known checkpoints including PD-1 CTLA-4 successfully targeted blocking antibodies immunotherapy. Here, we summarize changes role play immunity. We also focus potential ways target these sialoglycans order improve anti-cancer

Language: Английский

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