Evidence mapPaperPMID 39813162Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

Proximity Labeling and Genetic Screening Reveal that DSG2 is a Counter Receptor of Siglec-9 and Suppresses Macrophage Phagocytosis.

Ying Wu, Yuyu You, Tingsong Jiang, Yuqi He, Qingchi Fan, Xinlei Zeng, Ting Li, Yuxing Lu, Liang Qi, Fengxia Zhou and 6 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Ying WuSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
Yuyu YouSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
Tingsong JiangSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
Yuqi HeSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
Qingchi FanSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
Xinlei ZengSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
Ting LiSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
Yuxing LuSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
Liang QiSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
Fengxia ZhouSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
Lingyu SunSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
Danyang WangState Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510275, China.
Yong ZouDepartment of Blood Transfusion, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510000, China.
Guigen ZhangInstitute of Human Virology, Department of Pathogen Biology and Biosecurity, and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
Yanqiu YuanSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.ORCID https://orcid.org/0000-0001-8360-4843
Yang MaoSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.ORCID https://orcid.org/0000-0002-9674-1158

Funding

Guangdong Provincial Key Laboratory of Drug Nonclinical Evaluation and Research 2023B1212070029National Key R&D Program of Ministry of Science and Technology of China 2021YFA1200903National Natural Science Foundation of China 32271497National Natural Science Foundation of China 92478126National Natural Science Foundation of China T2450074Science and Technology Projects in Guangzhou 202103000029
6 · The paper itself

Abstract

Cancer cells present sialylated glycoconjugates that modulate the activity of various immune cells within the tumor microenvironment through trans interaction with immunosuppressive Siglec receptors. Identifying counter receptors for Siglecs can provide valuable targets for cancer immunotherapy, but it presents significant challenges. Here, the identification of DSG2 (Desmoglein 2) as a dominant counter receptor of Siglec-9 in melanoma cells is reported, using a workflow that combines the strength of proximity labeling and the advantage of CRISPR knockout screening. It is further demonstrated that the interaction between DSG2 and Siglec-9 is mainly dependent on sialic acid-bearing N-glycans on DSG2. Importantly, blocking trans interaction between DSG2 and Siglec-9 significantly enhances macrophage phagocytosis of melanoma cells and, to a lesser extent, other cancer cells. The work thus suggests sialylated DSG2 as a potential "don't eat me" signal molecule with therapeutic potentials in cancer immunotherapy.

Indexed as

Antigens, CDDesmoglein 2MacrophagesMelanomaPhagocytosisSialic Acid Binding Immunoglobulin-like LectinsAnimalsCell Line, TumorGenetic TestingHumansTumor MicroenvironmentAntigens, CDDesmoglein 2DSG2 protein, humanSialic Acid Binding Immunoglobulin-like LectinsSIGLEC9 protein, humanDSG2genetic screeningphagocytosisproximity labelingsiglec‐9

Identifiers

PMID39813162
PMCPMC11884560

What Socratic holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.