The recombinant human SIGLEC9 protein is a biologically active construct produced in a mammalian expression system to ensure proper folding and glycosylation. It includes the extracellular domain spanning amino acids 18 to 348 and is tagged at the C-terminus with a 10xHis sequence for straightforward purification and detection. Supplied as a lyophilized powder, the recombinant SIGLEC9 protein demonstrates high purity, exceeding 95% as determined by SDS-PAGE. Functional activity is confirmed via ELISA, where immobilized SIGLEC9 at 2 μg/mL effectively binds to the anti-SIGLEC9 recombinant antibody (CSB-RA021303MA1HU), with an EC50 ranging from 1.033 to 1.429 ng/mL. These features support its use in immunological assays, receptor-ligand interaction studies, and therapeutic antibody validation targeting SIGLEC9.
SIGLEC9 is predominantly expressed on various immune cells, including macrophages, dendritic cells, and natural killer (NK) cells, where it functions primarily as an inhibitory receptor, influencing both innate and adaptive immunity. SIGLEC9 mainly modulates immune suppression in the tumor microenvironment. This inhibitory role is evident in various cancers, where SIGLEC9 contributes to immune evasion mechanisms employed by tumors to escape immune surveillance. For instance, Xu et al. noted that high expression levels of SIGLEC9 are associated with poor prognosis in gliomas, suggesting an immune suppressive environment conducive to tumor growth and progression [1]. Furthermore, Ochman et al. reported that SIGLEC9 expression correlates with immune cell infiltration and cytokine production, indicating its involvement in shaping the tumor immune microenvironment [2].
Additionally, SIGLEC9 is implicated in the negative regulation of NK cell activation. While NK cells are essential for anti-tumor immunity, their functions can be inhibited upon interaction with SIGLEC9's ligands, leading to reduced cytotoxic activity and cytokine secretion [3]. Studies suggest that blocking SIGLEC9-mediated inhibitory signals may enhance the effectiveness of cancer immunotherapy, highlighting its potential as a therapeutic target [4][5].
Moreover, SIGLEC9 has been linked to inflammatory conditions outside of oncology. Biddanda et al. described a genetic variant in SIGLEC9 that correlates with altered protein expression, which may represent an evolutionary response to different pathogen burdens among populations [6]. This implies that SIGLEC9 may also regulate innate immune responses during chronic inflammatory conditions or infections [7].
The role of SIGLEC9 intersects with various pathways involved in maintaining immune homeostasis. Research indicates that SIGLEC9 can modulate innate immune responses, suggesting its importance not only in cancer but also in chronic diseases such as asthma and chronic obstructive pulmonary disease (COPD) [8]. Its interactions with sialylated ligands on different cell types enable it to serve as both an immune checkpoint and a mediator of immune cell signaling [9][10].
References:
[1] H. Xu, Y. Feng, et al. High expression levels of siglec9 indicate poor outcomes of glioma and correlate with immune cell infiltration. Frontiers in Oncology, vol. 12, 2022. https://doi.org/10.3389/fonc.2022.878849
[2] B. Ochman, A. Kot, S. Mielcarska, et al. Association of siglec9 expression with cytokine expression, tumor grading, kras, nras, braf, pik3ca, akt gene mutations, and msi status in colorectal cancer. Current Issues in Molecular Biology, vol. 46, no. 12, p. 13617-13646, 2024. https://doi.org/10.3390/cimb46120814
[3] Y. Zheng, X. Ma, et al. The roles of siglec7 and siglec9 on natural killer cells in virus infection and tumour progression. Journal of Immunology Research, vol. 2020, p. 1-9, 2020. https://doi.org/10.1155/2020/6243819
[4] Y. Wu, W. Huang, et al. Siglec-9, a putative immune checkpoint marker for cancer progression across multiple cancer types. Frontiers in Molecular Biosciences, vol. 9, 2022. https://doi.org/10.3389/fmolb.2022.743515
[5] P. Schmassmann, J. Roux, et al. Targeting the siglec–sialic acid axis promotes antitumor immune responses in preclinical models of glioblastoma. Science Translational Medicine, vol. 15, no. 705, 2023. https://doi.org/10.1126/scitranslmed.adf5302
[6] A. Biddanda, K. Arce, et al. A survey of proteomic variation across two ethnic groups in nigeria and its relationship to obesity risk. 2022. https://doi.org/10.1101/2022.12.09.519773
[7] E. Orlova, J. Carlson, et al. Pilot gwas of caries in african-americans shows genetic heterogeneity. BMC Oral Health, vol. 19, no. 1, 2019. https://doi.org/10.1186/s12903-019-0904-4
[8] T. Ishii, T. Angata, et al. Influence of siglec9 polymorphisms on copd phenotypes including exacerbation frequency. Respirology, vol. 22, no. 4, p. 684-690, 2016. https://doi.org/10.1111/resp.12952
[9] B. Wang, Y. Zhu, et al. High siglec9 expression levels in cervical cancer correlate with immune cell infiltration. 2023. https://doi.org/10.21203/rs.3.rs-2974696/v1
[10] Z. Chen, M. Yu, et al. Tumor derived siglec family genes may play roles in tumor genesis, progression, and immune microenvironment regulation. Frontiers in Oncology, vol. 10, 2020. https://doi.org/10.3389/fonc.2020.586820
