{"doi":"10.1101/2020.02.26.966291","title":"Autotaxin impedes anti-tumor immunity by suppressing chemotaxis and tumor infiltration of CD8 <sup>+</sup> T cells","abstract":"Summary Autotaxin (ATX) is secreted by diverse cell types to produce lysophosphatidic acid (LPA) that regulates multiple biological functions via G protein-coupled receptors LPAR1-6. ATX/LPA promotes tumor cell migration and metastasis mainly via LPAR1; however, its actions in the tumor immune microenvironment remain unclear. Here, we show that ATX secreted by melanoma cells is chemorepulsive for tumor-infiltrating lymphocytes and circulating CD8 + T cells ex vivo , with ATX functioning as an LPA-producing chaperone. Mechanistically, T-cell repulsion predominantly involves G α 12/13 -coupled LPAR6. Upon anti-cancer vaccination of tumor-bearing mice, ATX does not affect the induction of systemic T-cell responses but suppresses tumor infiltration of cytotoxic CD8 + T cells and thereby impairs tumor regression. Moreover, single-cell data from patient samples are consistent with intra-tumor ATX acting as a T-cell repellent. These studies highlight an unexpected role for the pro-metastatic ATX-LPAR axis in suppressing CD8 + T-cell infiltration to impede anti-tumor immunity, suggesting new therapeutic opportunities.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":121981,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9588,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":562205,"name":"Elselien Frijlink","orcid":"0000-0002-9249-8074","position":1,"is_corresponding":false},{"id":562206,"name":"Irene van der Haar Àvila","orcid":"0000-0001-9679-8149","position":2,"is_corresponding":false},{"id":562207,"name":"Apostolos Menegakis","orcid":"0000-0003-1147-9806","position":3,"is_corresponding":false},{"id":562697,"name":"Maaike van Zon","orcid":null,"position":4,"is_corresponding":false},{"id":237991,"name":"Andrew J. Morris","orcid":"0000-0003-1910-4865","position":5,"is_corresponding":false},{"id":562208,"name":"Jan Köster","orcid":"0000-0002-0890-7585","position":6,"is_corresponding":false},{"id":562209,"name":"Fernando Salgado-Polo","orcid":"0000-0001-8362-5281","position":7,"is_corresponding":false},{"id":562210,"name":"Sander de Kivit","orcid":"0000-0003-0148-7802","position":8,"is_corresponding":false},{"id":562698,"name":"Telma Lança","orcid":null,"position":9,"is_corresponding":false},{"id":562211,"name":"Antonio Mazzocca","orcid":"0000-0003-0940-7352","position":10,"is_corresponding":false},{"id":210256,"name":"Zoë Johnson","orcid":"0000-0002-4120-2579","position":11,"is_corresponding":false},{"id":68943,"name":"John B.A.G. Haanen","orcid":"0000-0001-5884-7704","position":12,"is_corresponding":false},{"id":96340,"name":"Ton N. Schumacher","orcid":"0000-0003-0517-8804","position":13,"is_corresponding":false},{"id":117601,"name":"Anastassis Perrakis","orcid":"0000-0002-1151-6227","position":14,"is_corresponding":false},{"id":562212,"name":"Inge Verbrugge","orcid":"0000-0003-4298-061X","position":15,"is_corresponding":false},{"id":562213,"name":"Joost H. van den Berg","orcid":"0000-0002-4928-8397","position":16,"is_corresponding":false},{"id":329308,"name":"Jannie Borst","orcid":"0000-0002-8043-5009","position":17,"is_corresponding":false},{"id":562214,"name":"Wouter H. Moolenaar","orcid":"0000-0001-7545-198X","position":18,"is_corresponding":false},{"id":562204,"name":"Elisa Matas-Rico","orcid":"0000-0003-0640-5511","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-07-18T23:14:46.979435Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}