Siglec-9 Restrains Antibody-Dependent Natural Killer Cell Cytotoxicity against SARS-CoV-2

Saini, Pratima; Adeniji, Opeyemi S.; Bordoloi, Devivasha; Kinslow, Jennifer; Martinson, Jeff; Parent, Danielle; Hong, Kai Ying; Koshy, Jane; Kulkarni, Abhijeet J; Zilberstein, Netanel F; Balk, R.A.; Moy, James N.; Giron, Leila B.; Tracy, Russell P.; Keshavarzian, Ali; Muthumani, Kar; Landay, Alan; Weiner, David B.; Abdel‐Mohsen, Mohamed

doi:10.1128/mbio.03393-22

Cited by 7 publications

(3 citation statements)

References 55 publications

(76 reference statements)

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“…The high sensitivity suggests they can be promising biomarkers for COAD treatments. Future investigation of finding the interaction between them and their sialic-glycan ligands is therefore an important direction of research ( Sullivan-Chang et al, 2013 ; Gianchecchi et al, 2021 ; Laubli et al, 2022 ; Saini et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

Unveiling the hub genes in the SIGLECs family in colon adenocarcinoma with machine learning

Li,

Yao

2024

Front. Genet.

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BackgroundDespite the recognized roles of Sialic acid-binding Ig-like lectins (SIGLECs) in endocytosis and immune regulation across cancers, their molecular intricacies in colon adenocarcinoma (COAD) are underexplored. Meanwhile, the complicated interactions between different SIGLECs are also crucial but open questions.MethodsWe investigate the correlation between SIGLECs and various properties, including cancer status, prognosis, clinical features, functional enrichment, immune cell abundances, immune checkpoints, pathways, etc. To fully understand the behavior of multiple SIGLECs’ co-evolution and subtract its leading effect, we additionally apply three unsupervised machine learning algorithms, namely, Principal Component Analysis (PCA), Self-Organizing Maps (SOM), K-means, and two supervised learning algorithms, Least Absolute Shrinkage and Selection Operator (LASSO) and neural network (NN).ResultsWe find significantly lower expression levels in COAD samples, together with a systematic enhancement in the correlations between distinct SIGLECs. We demonstrate SIGLEC14 significantly affects the Overall Survival (OS) according to the Hazzard ratio, while using PCA further enhances the sensitivity to both OS and Disease Free Interval (DFI). We find any single SIGLEC is uncorrelated to the cancer stages, which can be significantly improved by using PCA. We further identify SIGLEC-1,15 and CD22 as hub genes in COAD through Differentially Expressed Genes (DEGs), which is consistent with our PCA-identified key components PC-1,2,5 considering both the correlation with cancer status and immune cell abundance. As an extension, we use SOM for the visualization of the SIGLECs and show the similarities and differences between COAD patients. SOM can also help us define subsamples according to the SIGLECs status, with corresponding changes in both immune cells and cancer T-stage, for instance.ConclusionWe conclude SIGLEC-1,15 and CD22 as the most promising hub genes in the SIGLECs family in treating COAD. PCA offers significant enhancement in the prognosis and clinical analyses, while using SOM further unveils the transition phases or potential subtypes of COAD.

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Section: Discussionmentioning

confidence: 99%

Unveiling the hub genes in the SIGLECs family in colon adenocarcinoma with machine learning

Li,

Yao

2024

Front. Genet.

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“…nABs are used to bind to one specific target site in the body and cause various changes to enact molecular mechanisms [ 215 ]. Viral S protein and glycoprotein are the main target of nABs [ 216 , 217 ]. As previously mentioned, SARS-CoV-2 and SARS-CoV have a high genetic similarity, especially since both have a similar RBD formation [ 218 ].…”

Section: Antiviral Therapy Against Covid-19mentioning

confidence: 99%

COVID‐19: An Overview of SARS‐CoV‐2 Variants—The Current Vaccines and Drug Development

Bostanghadiri,

Ziaeefar,

Mofrad

et al. 2023

BioMed Research International

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The world is presently in crisis facing an outbreak of a health-threatening microorganism known as COVID-19, responsible for causing uncommon viral pneumonia in humans. The virus was first reported in Wuhan, China, in early December 2019, and it quickly became a global concern due to the pandemic. Challenges in this regard have been compounded by the emergence of several variants such as B.1.1.7, B.1.351, P1, and B.1.617, which show an increase in transmission power and resistance to therapies and vaccines. Ongoing researches are focused on developing and manufacturing standard treatment strategies and effective vaccines to control the pandemic. Despite developing several vaccines such as Pfizer/BioNTech and Moderna approved by the U.S. Food and Drug Administration (FDA) and other vaccines in phase 4 clinical trials, preventive measures are mandatory to control the COVID-19 pandemic. In this review, based on the latest findings, we will discuss different types of drugs as therapeutic options and confirmed or developing vaccine candidates against SARS-CoV-2. We also discuss in detail the challenges posed by the variants and their effect on therapeutic and preventive interventions.

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“…Different activities of NK cells, including their critical role in immunosurveillance, makes them attractive candidates for OC therapy ( 8 ). NK functions are regulated by multiple signals transmitted by the receptors present on the cell surface, which include both activating and inhibitory receptors ( 7 , 9 ). One inhibitory receptor expressed on human NK cells is sialic acid (Sia)–binding immunoglobulin-like lectin-7 (Siglec-7) ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

Siglec-7 glyco-immune binding mAbs or NK cell engager biologics induce potent antitumor immunity against ovarian cancers

Bordoloi,

Kulkarni,

Adeniji

et al. 2023

Sci. Adv.

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Ovarian cancer (OC) is a lethal gynecologic malignancy, with modest responses to CPI. Engagement of additional immune arms, such as NK cells, may be of value. We focused on Siglec-7 as a surface antigen for engaging this population. Human antibodies against Siglec-7 were developed and characterized. Coculture of OC cells with PBMCs/NKs and Siglec-7 binding antibodies showed NK-mediated killing of OC lines. Anti–Siglec-7 mAb (DB7.2) enhanced survival in OC-challenged mice. In addition, the combination of DB7.2 and anti–PD-1 demonstrated further improved OC killing in vitro. To use Siglec-7 engagement as an OC-specific strategy, we engineered an NK cell engager (NKCE) to simultaneously engage NK cells through Siglec-7, and OC targets through FSHR. The NKCE demonstrated robust in vitro killing of FSHR + OC, controlled tumors, and improved survival in OC-challenged mice. These studies support additional investigation of the Siglec-7 targeting approaches as important tools for OC and other recalcitrant cancers.

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Siglec-9 Restrains Antibody-Dependent Natural Killer Cell Cytotoxicity against SARS-CoV-2

Abstract: One mechanism that cancer cells use to evade natural killer cell immune surveillance is by expressing high levels of sialoglycans, which bind to Siglec-9, a glyco-immune checkpoint molecule on NK cells. This binding inhibits NK cell cytotoxicity.

Cited by 7 publications

References 55 publications

Unveiling the hub genes in the SIGLECs family in colon adenocarcinoma with machine learning

Unveiling the hub genes in the SIGLECs family in colon adenocarcinoma with machine learning

COVID‐19: An Overview of SARS‐CoV‐2 Variants—The Current Vaccines and Drug Development

Siglec-7 glyco-immune binding mAbs or NK cell engager biologics induce potent antitumor immunity against ovarian cancers

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