Sialoglycans and Siglecs Can Shape the Tumor Immune Microenvironment

Wall, Stephanie van de; Santegoets, Kim C. M.; Houtum, Eline J.H. van; Büll, Christian; Adema, Gosse J.

doi:10.1016/j.it.2020.02.001

Cited by 149 publications

(111 citation statements)

References 70 publications

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“…Also, the recent study about SIGLEC15 additionally demonstrated the similar structure of SIGLEC15 and PDL1, which makes us wonder whether SIGLEC family genes expressed on tumor cells may directly influence immune cell infiltration and function in tumor microenvironment by binding to potential targets on immune cells, since SIGLEC15 has a relatively conservative structure among them ( 15 , 43 – 45 ). Those results shed new light on immune blockade therapy to improve patients’ prognosis by neutralizing SIGLEC receptors on tumor cells or immune cells ( 12 , 15 , 46 , 47 ).…”

Section: Discussionmentioning

confidence: 95%

“…It has been found that tumor cells can express sialylated ligands for SIGLEC receptors on immune cells, depressing immune cell function to escape immune surveillance, such as SIGLEC7 and SIGLEC9 on natural killer cell (7)(8)(9)(10)(11)(12). However, SIGLEC family genes can also be expressed by tumor cells across cancer types, and recently, studies have found SIGLEC15 expressed by tumor cells or macrophages in mouse melanoma model could directly depress CD8+ T cell infiltration and function in tumor microenvironment through binding to presumptive target on CD8+ T cells (13)(14)(15).…”

mentioning

confidence: 99%

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Tumor Derived SIGLEC Family Genes May Play Roles in Tumor Genesis, Progression, and Immune Microenvironment Regulation

Zheng

Guo

et al. 2020

Front. Oncol.

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Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

Tumor Derived SIGLEC Family Genes May Play Roles in Tumor Genesis, Progression, and Immune Microenvironment Regulation

Zheng

Guo

et al. 2020

Front. Oncol.

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“…16 Therefore, the Siglecs family of proteins have received increasing attention in tumor immunity. [14][15][16][17]26 An increasing number of Siglecs-or sialoglycan-targeted therapeutic drugs have been developed and may represent a potential novel immune-checkpoint. Targeting Siglec-15 may be an effective alternative therapy for patients that do not respond to PD-1/PD-L1 antibodies.…”

Section: Discussionmentioning

confidence: 99%

“… 13 In recent years, an increasing number of Siglec members have been found to play a crucial role in tumor immunosuppression. 14 – 16 Siglec-7 and Siglec-9 expressed on the surface of natural killer (NK) cells and interacting with sialoglycans on cancer cells inhibited NK cells cytolytic capacity. 17 , 18 Siglec-9 on T cells and tumor-associated macrophages (TAMs) also play a role in “immune checkpoints” leading to immune evasion.…”

Section: Introductionmentioning

confidence: 99%

Expression signature, prognosis value, and immune characteristics of Siglec-15 identified by pan-cancer analysis

Zhang

Wang

et al. 2020

OncoImmunology

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Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) is considered a novel anti-tumor target comparable to programmed cell death 1 ligand 1(PD-L1). However, little is known about Siglec-15. Our study aims to understand its expression signature, prognosis value, immune infiltration pattern, and biological function using multi-omic bioinformatics from public databases and verify them in lung cancer patients. Integrated analysis of The Cancer Genome Atlas and Genotype-Tissue Expression portals showed Siglec-15 was overexpressed across cancers. Genetic and epigenetic alteration analysis was performed using cBioportal and UALCAN, showed Siglec-15 was regulated at the genetic and epigenetic levels. Survival estimated using Kaplan-Meier plotter indicated high Siglec-15 expression correlated with favorable or unfavorable outcomes depending on the different type and subtype of cancer. Components of immune microenvironment were analyzed using CIBERSORT, and the correlation between immune cells and Siglec-15 was found to be distinct across cancer types. Based on Gene Set Enrichment Analysis, Siglec-15 was implicated in pathways involved in immunity, metabolism, cancer, and infectious diseases. Lung cancer patients with positive Siglec-15 expression showed significantly short survival rates in progressionfree survival concomitant with reduced infiltration of CD20 + B, and dendritic cells by immunohistochemistry. Quantitative real-time PCR results indicated the overexpression of Siglec-15 was correlated with activation of the chemokine signaling pathway. In conclusion, Siglec-15 could serve as a vital prognostic biomarker and play an immune-regulatory role in tumors. These results provide us with clues to better understand Siglec-15 from the perspective of bioinformatics and highlight the importance of Siglec-15 in many types of cancer.

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“…Moreover, the incorporation of the non-human sialic acid N-glycolyl-neuraminic acid (Neu5Gc) into glycans and the interaction with circulating anti-Neu5Gc antibodies influences cancer progression. [22][23][24][25][26] Neu5Gc is biosynthesized from N-acetyl-neuraminic acid (Neu5Ac) via the enzyme CMP-Neu5Ac hydroxylase (CMAH), which is not present in humans. 27 However, various studies have found an increased presence of Neu5Gc-containing glycans in cancer, which could be associated with uptake of meat from Neu5Gc producing mammals.…”

Section: Changes In Sialylationmentioning

confidence: 99%

Tumor-associated carbohydrates and immunomodulatory lectins as targets for cancer immunotherapy

Mantuano

Natoli

Zippelius

et al. 2020

J Immunother Cancer

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During oncogenesis, tumor cells present specific carbohydrate chains that are new targets for cancer immunotherapy. Whereas these tumor-associated carbohydrates (TACA) can be targeted with antibodies and vaccination approaches, TACA including sialic acid-containing glycans are able to inhibit anticancer immune responses by engagement of immune receptors on leukocytes. A family of immune-modulating receptors are sialic acid-binding Siglec receptors that have been recently described to inhibit antitumor activity mediated by myeloid cells, natural killer cells and T cells. Other TACA-binding receptors including selectins have been linked to cancer progression. Recent studies have shown that glycan-lectin interactions can be targeted to improve cancer immunotherapy. For example, interactions between the immune checkpoint T cell immunoglobulin and mucin-domain containing-3 and the lectin galectin-9 are targeted in clinical trials. In addition, an antibody against the lectin Siglec-15 is being tested in an early clinical trial. In this review, we summarize the previous and current efforts to target TACA and to inhibit inhibitory immune receptors binding to TACA including the Siglec-sialoglycan axis.

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Sialoglycans and Siglecs Can Shape the Tumor Immune Microenvironment

Cited by 149 publications

References 70 publications

Tumor Derived SIGLEC Family Genes May Play Roles in Tumor Genesis, Progression, and Immune Microenvironment Regulation

Tumor Derived SIGLEC Family Genes May Play Roles in Tumor Genesis, Progression, and Immune Microenvironment Regulation

Expression signature, prognosis value, and immune characteristics of Siglec-15 identified by pan-cancer analysis

Tumor-associated carbohydrates and immunomodulatory lectins as targets for cancer immunotherapy

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