{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wee Y"],"funding":["U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)","American Cancer Society","NCATS NIH HHS","NIAID NIH HHS","American Cancer Society (American Cancer Society, Inc.)","U.S. Department of Health & Human Services | NIH | National Cancer Institute","U.S. Department of Defense","U.S. Department of Defense (United States Department of Defense)","NCI NIH HHS"],"pagination":["6613"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11298541"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(1)"],"pubmed_abstract":["Tumour-host immune interactions lead to complex changes in the tumour microenvironment (TME), impacting progression, metastasis and response to therapy. While it is clear that cancer cells can have the capacity to alter immune landscapes, our understanding of this process is incomplete. Herein we show that endocytic trafficking at the plasma membrane, mediated by the small GTPase ARF6, enables melanoma cells to impose an immunosuppressive TME that accelerates tumour development. This ARF6-dependent TME is vulnerable to immune checkpoint blockade therapy (ICB) but in murine melanoma, loss of Arf6 causes resistance to ICB. Likewise, downregulation of ARF6 in patient tumours correlates with inferior overall survival after ICB. Mechanistically, these phenotypes are at least partially explained by ARF6-dependent recycling, which controls plasma membrane density of the interferon-gamma receptor. Collectively, our findings reveal the importance of endomembrane trafficking in outfitting tumour cells with the ability to shape their immune microenvironment and respond to immunotherapy."],"journal":["Nature communications"],"pubmed_title":["Tumour-intrinsic endomembrane trafficking by ARF6 shapes an immunosuppressive microenvironment that drives melanomagenesis and response to checkpoint blockade therapy."],"pmcid":["PMC11298541"],"funding_grant_id":["K08 CA188563","P30 CA042014","W81XWH2210910","P50 CA221703","R37CA230630-01A1","133649RSG1901901CSM","UM1 TR004409","R37 CA230630","R01 AI158710","R01 CA121118"],"pubmed_authors":["Stubben C","Rogers A","Boucher KM","Ekiz HA","Tong Z","Grossmann AH","Wee Y","Gopal YNV","Wilson EC","Holmen SL","Wang J","Oviedo JM","Wolff RK","Davies MA","Tay JKH","DeGroot E","Williams MA","Fairfax KC","Rich CP"],"additional_accession":[]},"is_claimable":false,"name":"Tumour-intrinsic endomembrane trafficking by ARF6 shapes an immunosuppressive microenvironment that drives melanomagenesis and response to checkpoint blockade therapy.","description":"Tumour-host immune interactions lead to complex changes in the tumour microenvironment (TME), impacting progression, metastasis and response to therapy. While it is clear that cancer cells can have the capacity to alter immune landscapes, our understanding of this process is incomplete. Herein we show that endocytic trafficking at the plasma membrane, mediated by the small GTPase ARF6, enables melanoma cells to impose an immunosuppressive TME that accelerates tumour development. This ARF6-dependent TME is vulnerable to immune checkpoint blockade therapy (ICB) but in murine melanoma, loss of Arf6 causes resistance to ICB. Likewise, downregulation of ARF6 in patient tumours correlates with inferior overall survival after ICB. Mechanistically, these phenotypes are at least partially explained by ARF6-dependent recycling, which controls plasma membrane density of the interferon-gamma receptor. Collectively, our findings reveal the importance of endomembrane trafficking in outfitting tumour cells with the ability to shape their immune microenvironment and respond to immunotherapy.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Aug","modification":"2026-06-01T15:24:37.995Z","creation":"2025-02-19T04:41:05.069Z"},"accession":"S-EPMC11298541","cross_references":{"pubmed":["39098861"],"doi":["10.1038/s41467-024-50881-1"]}}