Immunopositivity for Siglec-15 in gastric cancer and its association with clinical and pathological parameters

Quirino, Michael Williams Leal; Pereira, Michelly Cristiny; Souza, Maria de Fátima Deodato de; Pitta, Ivan da Rocha; Filho, Antônio Felix da Silva; Albuquerque, Mário S. de Souza; Albuquerque, Amanda Vasconcelos de; Martins, Mário Rino; Pitta, Maíra Galdino da Rocha; Rêgo, Moacyr Jesus Barreto de Melo

doi:10.4081/ejh.2021.3174

Cited by 15 publications

(15 citation statements)

References 33 publications

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“…In the present study, our findings also revealed that Siglec‐15 positivity was related to improved PFS and DSS, and was an independent predictor of prognosis in PDAC. In addition, a previous study demonstrated that Siglec‐15 expression was significantly more frequent in AJCC II stage and well‐differentiated gastric cancer [ 31 ], while positive expression of Siglec‐15 was associated with the presence of perineural invasion and well and moderate differentiation in our study. The pan‐cancer analysis and our data suggest that the expression of Siglec‐15 may have distinct prognostic implications in different types of cancer.…”

Section: Discussionsupporting

confidence: 73%

“…Li et al demonstrated that Siglec‐15 overexpression was associated with worse overall survival (OS) and relapse‐free survival (RFS) in kidney cancer, and they also found that Siglec‐15 was correlated with poor PFS, but not OS, in lung adenocarcinoma [ 30 ]. Quirino et al found that Siglec‐15 expression was not related to OS and RFS in gastric cancer [ 31 ], and Hao et al similarly demonstrated that Siglec‐15 was not associated with OS in early NSCLC [ 32 ]. In contrast, high Siglec‐15 expression was correlated with better OS in bladder cancer, invasive breast carcinoma, thyroid cancer, endometrioid carcinoma, and head and neck squamous cell carcinoma and with better RFS in ovarian cancer, liver cancer, and endometrioid carcinoma, which was consistent with our results in PDAC [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

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Analysis of a novel immune checkpoint, Siglec‐15, in pancreatic ductal adenocarcinoma

Chen

Zhang

et al. 2022

The Journal of Pathology CR

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Siglec‐15, a novel immune checkpoint, is an emerging target for next‐generation cancer immunotherapy. However, the role of Siglec‐15 in pancreatic ductal adenocarcinoma (PDAC) remains poorly understood. We investigated the expression of Siglec‐15 and its association with clinicopathological characteristics, programmed cell death‐ligand 1 (PD‐L1), immune cells, and DNA damage repair (DDR) molecules in a cohort of 291 patients with PDAC. Positive tumour cell expression of Siglec‐15 and PD‐L1 was observed in 18.6 and 30.3% of the samples, respectively. We also detected Siglec‐15 positivity in macrophages in 3.4% of patients. Co‐expression of Siglec‐15 with PD‐L1 was observed in 6.1% of the patients. A total of 33 PD‐L1‐negative samples (18.0%) were Siglec‐15‐positive. Siglec‐15 was observed more frequently in moderate‐to‐well‐differentiated tumours. Siglec‐15 was associated with a low density of Tregs and CD45RO T cells, high BRCA1 expression, and improved survival. Both Siglec‐15 and PD‐L1 are independent factors of patient outcomes. The prognostic significance of Siglec‐15 for survival was more discriminative in lymph node‐negative, high BRCA1 expression, or low BRCA2 expression tumours than in lymph node‐positive, low BRCA1 expression, or high BRCA2 expression tumours. In conclusion, we identified Siglec‐15 as a promising predictor for prognosis combined with different DDR molecular statuses and complex tumour‐infiltrating cells in PDAC. Targeting Siglec‐15 may be a novel therapeutic option for patients who are unresponsive to anti‐PD‐1 therapy. Future studies are needed to validate the prognostic significance of Siglec‐15 and to investigate its regulatory mechanisms in this disease.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Analysis of a novel immune checkpoint, Siglec‐15, in pancreatic ductal adenocarcinoma

Chen

Zhang

et al. 2022

The Journal of Pathology CR

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“…In Li et al, high Siglec-15 expression was associated with poor OS in GC (HR = 4.87, 95% CI = 1.42–15.4, p = 0.006) [ 163 ]. At the same time, in other studies, the expression of Siglec-15 in GC was not associated with OS [ 160 , 164 ].…”

Section: Immune Checkpoint Expression In Connection With Clinical Features and The Therapeutic Efficacy Of Their Inhibitionmentioning

confidence: 66%

“…Quirino et al reported the association of Siglec-15 expression with such clinicopathological characteristics as the TNM stage ( p = 0.01), histological grade ( p = 0.0022) and angiolymphatic invasion ( p = 0.041) [ 164 ].…”

Section: Immune Checkpoint Expression In Connection With Clinical Features and The Therapeutic Efficacy Of Their Inhibitionmentioning

confidence: 99%

Expression of Immune Checkpoints in Malignant Tumors: Therapy Targets and Biomarkers for the Gastric Cancer Prognosis

et al. 2021

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To increase the effectiveness of anticancer therapy based on immune checkpoint (IC) inhibition, some ICs are being investigated in addition to those used in clinic. We reviewed data on the relationship between PD-L1, B7-H3, B7-H4, IDO1, Galectin-3 and -9, CEACAM1, CD155, Siglec-15 and ADAM17 expression with cancer development in complex with the results of clinical trials on their inhibition. Increased expression of the most studied ICs—PD-L1, B7-H3, and B7-H4—is associated with poor survival; their inhibition is clinically significant. Expression of IDO1, CD155, and ADAM17 is also associated with poor survival, including gastric cancer (GC). The available data indicate that CD155 and ADAM17 are promising targets for immune therapy. However, the clinical trials of anti-IDO1 antibodies have been unsatisfactory. Expression of Galectin-3 and -9, CEACAM1 and Siglec-15 demonstrates a contradictory relationship with patient survival. The lack of satisfactory results of these IC inhibitor clinical trials additionally indicates the complex nature of their functioning. In conclusion, in many cases it is important to analyze the expression of other participants of the immune response besides target IC. The PD-L1, B7-H3, B7-H4, IDO1 and ADAM17 may be considered as candidates for prognosis markers for GC patient survival.

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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: 72%

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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Immunopositivity for Siglec-15 in gastric cancer and its association with clinical and pathological parameters

Cited by 15 publications

References 33 publications

Analysis of a novel immune checkpoint, Siglec‐15, in pancreatic ductal adenocarcinoma

Analysis of a novel immune checkpoint, Siglec‐15, in pancreatic ductal adenocarcinoma

Expression of Immune Checkpoints in Malignant Tumors: Therapy Targets and Biomarkers for the Gastric Cancer Prognosis

Siglec Signaling in the Tumor Microenvironment

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