Proximity Labeling and Genetic Screening Reveal that DSG2 is a Counter Receptor of Siglec‐9 and Suppresses Macrophage Phagocytosis
Source abstract
Abstract
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.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Galectins and Cancer Biology · Cellular transport and secretion · Phagocytosis and Immune Regulation
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
School of Pharmaceutical Sciences Sun Yat‐sen University Guangzhou 510006 China
State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat‐sen University Cancer Center Guangzhou 510275 China
Department of Blood Transfusion The Third Affiliated Hospital of Sun Yat‐sen University Guangzhou 510000 China
Institute 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
State Key Laboratory of Anti‐Infective Drug Discovery and Development School of Pharmaceutical Sciences Sun Yat‐sen University Guangzhou 510006 China
Guangdong Provincial Key Laboratory of Drug Non‐Clinical Evaluation and Research Guangzhou 510006 China
Funding
National Natural Science Foundation of China
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