{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:22:07Z","timestamp":1790184127768,"version":"4.1.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P01 CA084203, R01 CA260340, R01 CA231606, 5R01CA260340-02, 1R01EB034360-01A1, R01 CA272876"],"award-info":[{"award-number":["P01 CA084203, R01 CA260340, R01 CA231606, 5R01CA260340-02, 1R01EB034360-01A1, R01 CA272876"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["FA 9550-17-1-0277"],"award-info":[{"award-number":["FA 9550-17-1-0277"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Photodynamic priming (PDP), a fallout of photodynamic therapy, transiently modulates the tumor microenvironment (TME), enhances therapeutic susceptibility, and promotes immunogenic cell death through the release of damage-associated molecular patterns (DAMPs). Pancreatic ductal adenocarcinoma (PDAC) remains non-responsive to current therapies with a desmoplastic and immunosuppressive TME that limits drug delivery and blunts responses to immune checkpoint blockade. We investigated whether PDP could enhance anti-PD1 therapy responses in PDAC using patient-derived organoids (PDOs). PDOs were treated with Visudyne and red light (25, 75, and 100 J\/cm\u00b2), followed by assessment of cytotoxicity, DAMP expression (HSP60, calreticulin, HMGB1), and transcriptomic changes. Monocyte-derived dendritic cells (mDCs) from healthy donors were cocultured with PDP-treated (25 J\/cm\n                    <jats:sup>2<\/jats:sup>\n                    ) PDOs, then with matched na\u00efve T cells. mDC and T cell activation markers were analyzed. Pembrolizumab (anti-PD1) was added to PDO-mDC-T cell cocultures to evaluate combined effects on PDO viability and T cell activation. PDP induced dose-dependent cytotoxicity and upregulated DAMPs. Gene profiling in PDOs showed increased\n                    <jats:italic>IFN-\u03b3<\/jats:italic>\n                    ,\n                    <jats:italic>TNF-\u03b1<\/jats:italic>\n                    , and\n                    <jats:italic>CXCL12<\/jats:italic>\n                    , with reduced\n                    <jats:italic>PD-L1<\/jats:italic>\n                    ,\n                    <jats:italic>TGF-\u03b21<\/jats:italic>\n                    , and\n                    <jats:italic>FOXP1<\/jats:italic>\n                    expression. mDCs exposed to PDP-treated PDOs upregulated CD40, CD86, and MHC-II, driving activation of CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, evidenced by elevated PD1 expression. Addition of pembrolizumab further decreased PDO viability and amplified effector cytokines (\n                    <jats:italic>IFN-\u03b3<\/jats:italic>\n                    ,\n                    <jats:italic>TNF-\u03b1<\/jats:italic>\n                    ,\n                    <jats:italic>FASLG<\/jats:italic>\n                    ,\n                    <jats:italic>granzyme<\/jats:italic>\n                    B,\n                    <jats:italic>IL-2<\/jats:italic>\n                    ,\n                    <jats:italic>IL-21<\/jats:italic>\n                    ). PDP was associated with modulation of the PDAC TME toward a more immunogenic phenotype by enhancing tumor immunogenicity, activating dendritic cells and T cells, and potentiating PD1 blockade. These findings provide mechanistic support for further preclinical and clinical evaluation of PDP combined with checkpoint inhibition in PDAC.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1805948","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T05:38:30Z","timestamp":1786426710000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Photodynamic priming enhances anti-PD1 therapy responses in patient-derived pancreatic cancer organoid immune cocultures"],"prefix":"10.3389","volume":"17","author":[{"given":"Pushpamali","family":"De Silva","sequence":"first","affiliation":[{"name":"Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demi","family":"Wekking","sequence":"additional","affiliation":[{"name":"Wellman Center for 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