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Here, we show that in addition to its previously known effects, 5FU enhances PDT\u2010induced tumor\u2010regressing immunity. Murine actinic keratoses were treated with topical 5FU or vehicle for 3\u2009days prior to aminolevulinic acid application, followed by blue light illumination (~417\u2009nm). Lesions were harvested for time\u2010course analyses of innate immune cell recruitment into lesions, <jats:italic>i.e.<\/jats:italic> neutrophils (Ly6G+) and macrophages (F4\/80+), which peaked at 72\u2009h and 1\u2009week post\u2010PDT, respectively, and were greater in 5FU\u2010treated lesions. Enhanced infiltration of activated T cells (CD3+) throughout the time course, and of cytotoxic T cells (CD8+) at 1\u20132\u2009weeks post\u2010PDT, also occurred in 5FU\u2010treated lesions. 5FU pretreatment reduced the presence of cells expressing the immune checkpoint marker PD\u20101 at ~72\u2009h post\u2010PDT, favoring cytotoxic T cell activity. A combination of 5FU and PDT, each individually known to induce long\u2010term tumor\u2010targeting immune responses in addition to their more immediate effects on cancer cells, may synergize to provide better management of squamous precancers.<\/jats:p>","DOI":"10.1111\/php.13706","type":"journal-article","created":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T07:28:14Z","timestamp":1661844494000},"page":"437-447","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Combination of <scp>5\u2010Fluorouracil<\/scp> with Photodynamic Therapy: Enhancement of Innate and Adaptive Immune Responses in a Murine Model of Actinic Keratosis<sup>\u2020<\/sup>"],"prefix":"10.1111","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1893-8561","authenticated-orcid":false,"given":"Sanjay","family":"Anand","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Lerner Research Institute Cleveland Clinic  Cleveland OH USA"},{"name":"Dermatology and Plastic Surgery Institute Cleveland Clinic  Cleveland OH USA"},{"name":"Cleveland Clinic Lerner College of Medicine Cleveland Clinic  Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren E.","family":"Heusinkveld","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Lerner College of Medicine Cleveland Clinic  Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng\u2010En","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Lerner Research Institute Cleveland Clinic  Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lefatshe","family":"Lefatshe","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Lerner Research Institute Cleveland Clinic  Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pushpamali","family":"De Silva","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine Massachusetts General Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tayyaba","family":"Hasan","sequence":"additional","affiliation":[{"name":"Wellman Center for Photomedicine Massachusetts General Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3690-8382","authenticated-orcid":false,"given":"Edward V.","family":"Maytin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Lerner Research Institute Cleveland Clinic  Cleveland OH USA"},{"name":"Dermatology and Plastic Surgery Institute Cleveland Clinic  Cleveland OH USA"},{"name":"Cleveland Clinic Lerner College of Medicine Cleveland Clinic  Cleveland OH USA"},{"name":"Wellman Center for Photomedicine Massachusetts General Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,9,20]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21654"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph14050447"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389201003378979"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1074"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006416410198"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12061641"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1053-4296(97)80023-9"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-16-0608"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1997.164"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2013.67"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.27713"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-010-0479-7"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032712-100008"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.2174\/156652411795976574"},{"key":"e_1_2_6_16_1","article-title":"Myeloid derived suppressor cells\u2010an overview of combat strategies to increase immunotherapy efficacy","volume":"4","author":"Draghiciu O.","year":"2015","journal-title":"Onco. 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