{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T08:53:38Z","timestamp":1773392018837,"version":"3.50.1"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100031365","name":"Oslo universitetssykehus HF","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100031365","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Resistance to immune checkpoint inhibitors (ICIs) targeting the programmed cell death protein 1\/programmed death ligand 1 (PD\u20131\/PD\u2013L1) axis remains a major obstacle in non\u2013small cell lung cancer (NSCLC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>To address this, we investigated photochemical internalization (PCI), a light\u2013controlled endosomal escape technology, as a strategy to enhance intracellular delivery and efficacy of a PD\u2013L1\u2013targeted immunotoxin (anti\u2013PD\u2013L1\u2013SAP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      NSCLC cell lines with high (NCI\u2013H1975) and low (A549) PD\u2013L1 expression were subjected to PCI, resulting in a pronounced increase in cytotoxicity with picomolar potency (30 pM), while A549 cells required a higher dose (1000 pM) for a similar effect. Specificity was confirmed via receptor blockade and non\u2013targeted controls. Confocal microscopy demonstrated lysosomal and endosomal localization of anti\u2013PD\u2013L1\u2013SAP, and flow cytometry showed time\u2013dependent intracellular accumulation, consistent with PCI\u2019s requirement for endosomal sequestration prior to light\u2013induced release. Importantly, co\u2013treatment with the immune checkpoint inhibitor atezolizumab (Tecentriq\n                      <jats:sup>\u00ae<\/jats:sup>\n                      ) reduced PCI efficacy in PD\u2013L1^\n                      <jats:sup>high<\/jats:sup>\n                      ^ cells, underscoring the importance of receptor accessibility.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings demonstrate that PCI enhances delivery and activity of PD\u2013L1\u2013targeted biologics and may help overcome resistance mechanisms. Overall, PCI expands the therapeutic window of PD\u2013L1\u2013targeted immunotoxins and may complement current immunotherapies, supporting further preclinical evaluation in NSCLC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1750003","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T06:47:13Z","timestamp":1773384433000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Photochemical enhancement of PD-L1-SAP immunotoxin efficacy in non-small cell lung cancer cell lines"],"prefix":"10.3389","volume":"17","author":[{"given":"Magdal\u00e9na","family":"Kozl\u00edkov\u00e1","sequence":"first","affiliation":[{"name":"Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Kr\u00e1lov\u00e9, Charles University","place":["Hradec Kr\u00e1lov\u00e9, Czechia"]},{"name":"Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital","place":["Oslo, Norway"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inger Kristine Fjeldskaar","family":"Aukrust","sequence":"additional","affiliation":[{"name":"Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital","place":["Oslo, Norway"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monika","family":"Rohl\u00ed\u010dkov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Kr\u00e1lov\u00e9, Charles University","place":["Hradec Kr\u00e1lov\u00e9, Czechia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miloslav","family":"Mach\u00e1\u010dek","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Kr\u00e1lov\u00e9, Charles University","place":["Hradec Kr\u00e1lov\u00e9, Czechia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristian","family":"Berg","sequence":"additional","affiliation":[{"name":"Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital","place":["Oslo, Norway"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anette","family":"Weyergang","sequence":"additional","affiliation":[{"name":"Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital","place":["Oslo, Norway"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P\u00e5l Kristian","family":"Selbo","sequence":"additional","affiliation":[{"name":"Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital","place":["Oslo, 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