Sialic acid-binding immunoglobulin-like lectin-15 expression on peritumoral macrophages is a favorable prognostic factor for primary central nervous system lymphoma patients

Fudaba, Hirotaka; Momii, Yasutomo; Hirakawa, Taisei; Onishi, Kouhei; Asou, Daigo; Matsushita, Wataru; Kawasaki, Yukari; Sakai, Kenji; Fujiki, Minoru

doi:10.1038/s41598-020-79742-9

Cited by 21 publications

(18 citation statements)

References 24 publications

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“…21 Fubada et al have also demonstrated that the overexpression of Siglec-15 is indicative of a good prognosis for patients with primary central nervous system lymphoma. 22 Our ndings showed that Siglec-15 overexpression was related to an increase in the distant metastasis rate of NPC patients, which may be attributable to the fact that Siglec-15-mediated immune escape promotes the malignant biological behavior of tumor cells. Furthermore, our results showed that there was a negative correlation between the expression of Siglec-15 and PD-L1; hence, we further explored whether the combination of PD-L1 and Siglec-15 had an impact on the survival rate of NPC patients.…”

Section: Discussionmentioning

confidence: 70%

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Prognostic Value of PD-L1 and Siglec-15 Expression in Patients with Nasopharyngeal Carcinoma

Zhao¹,

Yang

Hu³

et al. 2021

Preprint

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Purpose: Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) might be involved in the activation of important pathways related to tumor immune escape, along with programmed death-ligand 1 (PD-L1). We aimed to investigate the correlation between the expression of Siglec-15 and PD-L1 in NPC patients.Patients and methods: We determined the expression of PD-L1 via immunohistochemical staining and that of Siglec-15 via immunofluorescent staining in 182 NPC tissue samples.Results: A significant correlation was identified between the PD-L1 and Siglec-15 expression (P=0.000). Moreover, Kaplan–Meier survival curves showed that PD-L1 expression were associated with improved overall survival (P=0.025) and Siglec-15 expression were associated with improved distant failure-free survival (P=0.048). Meanwhile, multivariate Cox analysis showed that PD-L1 and Siglec-15 were independent predictors of overall survival (P=0.020) and distant failure-free survival (P=0.047), respectively. The results of the log-rank test and Cox regression analyses showed that patients exhibiting no PD-L1/Siglec-15 expression were found to have significant advantages with regard to overall survival, compared to other groups (P=0.037).Conclusion: PD-L1 and Siglec-15 may represent novel biomarkers for predicting NPC patient prognosis. Siglec-15 could be considered as a potential target for the development of therapeutics for NPC treatment in the future.

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Section: Discussionmentioning

confidence: 70%

“…21 Fudaba et al have also shown that the detection of Siglec-15 in patients with primary CNS lymphoma was indicative of a good prognosis. 22 However, the relationship between Siglec-15 expression and NPC patient prognosis has not been identi ed in the current study.…”

Section: Introductionmentioning

confidence: 79%

Prognostic Value of PD-L1 and Siglec-15 Expression in Patients with Nasopharyngeal Carcinoma

Zhao¹,

Yang

Hu³

et al. 2021

Preprint

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“…Next to its expression on myeloid cells, Siglec-15 was observed on stromal cells and even on tumor cells (28). Siglec-15 expression on tumor cells was verified by others on several types of cancer, such as lymphoma, gastric cancer and acute myeloid leukemia (29)(30)(31). Similarly, Siglec-8 has been reported to be expressed by breast cancer cells (32).…”

Section: Siglec Expression Within the Tmementioning

confidence: 69%

Siglec Signaling in the Tumor Microenvironment

et al. 2021

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Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of receptors that recognize sialoglycans – sialic acid containing glycans that are abundantly present on cell membranes. Siglecs are expressed on most immune cells and can modulate their activity and function. The majority of Siglecs contains immune inhibitory motifs comparable to the immune checkpoint receptor PD-1. In the tumor microenvironment (TME), signaling through the Siglec-sialoglycan axis appears to be enhanced through multiple mechanisms favoring tumor immune evasion similar to the PD-1/PD-L1 signaling pathway. Siglec expression on tumor-infiltrating immune cells appears increased in the immune suppressive microenvironment. At the same time, enhanced Siglec ligand expression has been reported for several tumor types as a result of aberrant glycosylation, glycan modifications, and the increased expression of sialoglycans on proteins and lipids. Siglec signaling has been identified as important regulator of anti-tumor immunity in the TME, but the key factors contributing to Siglec activation by tumor-associated sialoglycans are diverse and poorly defined. Among others, Siglec activation and signaling are co-determined by their expression levels, cell surface distribution, and their binding preferences for cis- and trans-ligands in the TME. Siglec binding preference are co-determined by the nature of the proteins/lipids to which the sialoglycans are attached and the multivalency of the interaction. Here, we review the current understanding and emerging conditions and factors involved in Siglec signaling in the TME and identify current knowledge gaps that exist in the field.

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“…More recently, high Siglec-15 was also found to promote osteosarcoma progression via the activation of the DUSP1/MAPK signaling pathway [152], and hepatocellular carcinoma migration via CD44 interaction, which prevented lysosomal degradation [153]. As Siglec-15 is mutually exclusive to PD-L1, it is now emerging as a novel immune inhibitor for anti-PD-1/PD-L1 resistant patients [154,155].…”

Section: Siglec-15mentioning

confidence: 99%

Siglecs as Therapeutic Targets in Cancer

Lim

Sari-Ak

Bagga

2021

Biology

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Hypersialylation is a common post-translational modification of protein and lipids found on cancer cell surfaces, which participate in cell-cell interactions and in the regulation of immune responses. Sialic acids are a family of nine-carbon α-keto acids found at the outermost ends of glycans attached to cell surfaces. Given their locations on cell surfaces, tumor cells aberrantly overexpress sialic acids, which are recognized by Siglec receptors found on immune cells to mediate broad immunomodulatory signaling. Enhanced sialylation exposed on cancer cell surfaces is exemplified as “self-associated molecular pattern” (SAMP), which tricks Siglec receptors found on leukocytes to greatly down-regulate immune responsiveness, leading to tumor growth. In this review, we focused on all 15 human Siglecs (including Siglec XII), many of which still remain understudied. We also highlighted strategies that disrupt the course of Siglec-sialic acid interactions, such as antibody-based therapies and sialic acid mimetics leading to tumor cell depletion. Herein, we introduced the central roles of Siglecs in mediating pro-tumor immunity and discussed strategies that target these receptors, which could benefit improved cancer immunotherapy.

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Sialic acid-binding immunoglobulin-like lectin-15 expression on peritumoral macrophages is a favorable prognostic factor for primary central nervous system lymphoma patients

Cited by 21 publications

References 24 publications

Prognostic Value of PD-L1 and Siglec-15 Expression in Patients with Nasopharyngeal Carcinoma

Prognostic Value of PD-L1 and Siglec-15 Expression in Patients with Nasopharyngeal Carcinoma

Siglec Signaling in the Tumor Microenvironment

Siglecs as Therapeutic Targets in Cancer

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