{"doi":"10.1073/pnas.2107424118","title":"Siglecs-7/9 function as inhibitory immune checkpoints in vivo and can be targeted to enhance therapeutic antitumor immunity","abstract":"<jats:title>Significance</jats:title>\n                  <jats:p>Targeting myeloid cells represents a promising strategy to augment antitumor immunity and overcome resistance to existing T cell-targeting therapies. However myeloid checkpoints that can be effectively used as immunotherapy targets are still lacking. Here, we demonstrate the therapeutic potential of targeting Siglec-7 and Siglec-9 to enhance antitumor immunity in vivo. Using an immunocompetent mouse model humanized for Siglec-7/9, we show that these receptors inhibit the endogenous antitumor immune response in a tissue-specific manner. These Siglecs also restrict the response to tumor-targeting and checkpoint-targeting antibodies, highlighting their significance in combinatorial approaches to immunotherapy. Finally, we show that Siglec-7/9 blockade can significantly reduce tumor burden in vivo, supporting the use of antibodies targeting Siglec-7/9 to therapeutically enhance antitumor immunity.</jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2021,"id":622571,"datarank":0.7781078708761133,"base_score":5.187385805840755,"endowment":5.187385805840755,"self_citation_contribution":0.7781078708761133,"citation_network_contribution":0.0,"self_endowment_contribution":0.7781078708761133,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":178,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":10,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1327020,"name":"Polina Weitzenfeld","orcid":"0000-0001-7044-115X","position":1,"is_corresponding":false},{"id":723378,"name":"Patrick Smith","orcid":"0000-0003-2017-5468","position":2,"is_corresponding":false},{"id":109914,"name":"Jeffrey V. Ravetch","orcid":"0000-0003-2024-9041","position":3,"is_corresponding":false},{"id":984228,"name":"Itziar Ibarlucea-Benitez","orcid":"0000-0001-5756-5158","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Siglecs-7/9 function as inhibitory immune checkpoints in vivo and can be targeted to enhance therapeutic antitumor immunity","abstract":"<jats:title>Significance</jats:title>\n                  <jats:p>Targeting myeloid cells represents a promising strategy to augment antitumor immunity and overcome resistance to existing T cell-targeting therapies. However myeloid checkpoints that can be effectively used as immunotherapy targets are still lacking. Here, we demonstrate the therapeutic potential of targeting Siglec-7 and Siglec-9 to enhance antitumor immunity in vivo. Using an immunocompetent mouse model humanized for Siglec-7/9, we show that these receptors inhibit the endogenous antitumor immune response in a tissue-specific manner. These Siglecs also restrict the response to tumor-targeting and checkpoint-targeting antibodies, highlighting their significance in combinatorial approaches to immunotherapy. Finally, we show that Siglec-7/9 blockade can significantly reduce tumor burden in vivo, supporting the use of antibodies targeting Siglec-7/9 to therapeutically enhance antitumor immunity.</jats:p>","is_dataset_classified":null,"base_score":5.187385805840755,"endowment":5.187385805840755,"datacite_reuse_total":10,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"34155121","pmcid":"PMC8256000","openalex_id":"https://openalex.org/W3174289113","authors":[],"funders":[{"funder_name":"HHS | NIH | National Cancer Institute","grant_id":"R35CA196620","title":null},{"funder_name":"HHS | NIH | National Cancer Institute","grant_id":"R01CA244327","title":null},{"funder_name":"The Kimberly Lawrence-Netter Cancer Research Discovery 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receptors and signaling","Animals","Antibodies","Antigens, CD","Cell Line, Tumor","Cell Proliferation","Disease Progression","Humans","Immune Checkpoint Inhibitors","Immunity","Mice, Inbred C57BL","Mice, Knockout","Models, Biological","Neoplasms","Phenotype","Sialic Acid Binding Immunoglobulin-like Lectins","Tumor Microenvironment","Mice"],"mesh_terms":["Immune Checkpoint Inhibitors","Animals","Antibodies","Humans","Immunity","Mice, Inbred C57BL","Models, Biological","Neoplasms","Phenotype","Antigens, CD","Mice, Knockout","Disease Progression","Cell Line, Tumor","Cell Proliferation","Mice","Tumor Microenvironment","Sialic Acid Binding Immunoglobulin-like Lectins"],"keywords":["SIGLEC","Immunotherapy","In vivo","Immune system","Immunity","Myeloid","Cancer research","Blockade","Immunology","Immune checkpoint","Biology","Receptor","checkpoint","Fc receptor","Cancer Immunotherapy","Siglecs","Sialoglycan"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and 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