{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T02:15:30Z","timestamp":1787883330867,"version":"build-2784847793"},"reference-count":75,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:p>Several tumors have evolved the ability to evade the immune system by expressing programmed death ligand 1 (PD\u2010L1; also known as programmed cell death 1 ligand 1) on the membrane of neoplastic cells. PD\u2010L1 binds the receptor programmed cell death protein 1 (PD\u20101) on T\u00a0cells, deactivating the immune response. Accordingly, PD\u2010L1 has recently become a crucial target for cancer therapy. Yet, the molecular organization of PD\u2010L1 on the membrane is still rather obscure. Here, we investigated the plasma membrane organization of PD\u2010L1 by a multiscale fluorescence imaging toolbox reaching the nanoscale by super\u2010resolution microscopy. Our results indicate that a major fraction of PD\u2010L1 is largely engaged in membrane nanodomains of 25\u2009nm mean radius, which in turn organize in an irregular mesoscopic lattice with mean interdomain distance of about 180\u2009nm. The significant colocalization of PD\u2010L1 with lipid raft markers, which we assessed from 200 to 250\u2009nm down to &lt;\u200910\u2009nm, supports a raft\u2010driven organization of PD\u2010L1, which may follow its extended palmitoylation upon expression. This pattern was also demonstrated in living cells by visualizing PD\u2010L1 diffusion at different spatial scales. The raft\u2010orchestrated multiscale PD\u2010L1 organization on the cell membrane may afford novel targets for improved immuno\u2010oncology strategies.<\/jats:p>","DOI":"10.1111\/febs.70238","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T10:09:59Z","timestamp":1755857399000},"page":"5979-5997","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Nanoscale engagement of programmed death ligand 1 (\n                    <scp>PD<\/scp>\n                    \u2010\n                    <scp>L1<\/scp>\n                    ) in membrane lipid raft domains of cancer cells"],"prefix":"10.1111","volume":"292","author":[{"given":"Simone","family":"Civita","sequence":"first","affiliation":[{"name":"Department of Mathematical, Physical and Computer Sciences University of Parma  Parma Italy"},{"name":"Nanoscopy and NIC@IIT Istituto Italiano di Tecnologia  Genoa Italy"},{"name":"Department of Surgical, Medical and Molecular Pathology, and Critical Care Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Ruglioni","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical and Molecular Pathology, and Critical Care Medicine University of Pisa  Pisa Italy"},{"name":"Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Mariangeli","sequence":"additional","affiliation":[{"name":"Department of Mathematical, Physical and Computer Sciences University of Parma  Parma Italy"},{"name":"Nanoscopy and NIC@IIT Istituto Italiano di Tecnologia  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Barachini","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziano","family":"Salvadori","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical and Molecular Pathology, and Critical Care Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Cristiani","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical and Molecular Pathology, and Critical Care Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittoria","family":"Carnicelli","sequence":"additional","affiliation":[{"name":"Department of Surgical, Medical and Molecular Pathology, and Critical Care Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iacopo","family":"Petrini","sequence":"additional","affiliation":[{"name":"Department of Translational Research &amp; New Technologies in Surgery and Medicine University of Pisa and Azienda Ospedaliero Universitaria Pisana  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Nepita","sequence":"additional","affiliation":[{"name":"Nanoscopy and NIC@IIT Istituto Italiano di Tecnologia  Genoa Italy"},{"name":"Genoa Instruments s.r.l.  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