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To better understand how p\u2010PDT works, hairless mice with UV\u2010induced AK were treated with p\u2010PDT and monitored for 2\u00a0weeks. Lesion clearance after p\u2010PDT was similar to clearance after conventional PDT (c\u2010PDT). However, lesion biopsies showed minimal cell death and less production of reactive oxygen species (ROS) in p\u2010PDT treated than in c\u2010PDT\u2010treated lesions. Interestingly, p\u2010PDT triggered vigorous recruitment of immune cells associated with innate immunity. Neutrophils (Ly6G+) and macrophages (F4\/80+) appeared at 4\u00a0h and peaked at 24\u00a0h after p\u2010PDT. Damage\u2010associated molecular patterns (DAMPs), including calreticulin, HMGB1, and HSP70, were expressed at maximum levels around 24\u00a0h post\u2010p\u2010PDT. Total T cells (CD3+) were increased at 24\u00a0h, whereas large increases in cytotoxic (CD8+) and regulatory (Foxp3+) T cells were observed at 1 and 2\u00a0weeks post\u2010p\u2010PDT. In summary, the ability of p\u2010PDT to eliminate AK lesions, despite very little overt cellular damage, appears to involve stimulation of a local immune response.<\/jats:p>","DOI":"10.1111\/php.13350","type":"journal-article","created":{"date-parts":[[2020,10,28]],"date-time":"2020-10-28T21:03:22Z","timestamp":1603919002000},"page":"607-617","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Painless Photodynamic Therapy Triggers Innate and Adaptive Immune Responses in a Murine Model of UV\u2010induced Squamous Skin Pre\u2010cancer"],"prefix":"10.1111","volume":"97","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 of CWRU Cleveland Clinic  Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mukul","family":"Govande","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Lerner Research Institute, Cleveland Clinic  Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anton","family":"Yasinchak","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Lerner Research Institute, Cleveland Clinic  Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren","family":"Heusinkveld","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Lerner College of Medicine of CWRU Cleveland Clinic  Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sajina","family":"Shakya","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Lerner Research Institute, Cleveland Clinic  Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert L.","family":"Fairchild","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Lerner College of Medicine of CWRU Cleveland Clinic  Cleveland OH USA"},{"name":"Department of Inflammation and Immunity Lerner Research Institute Cleveland Clinic  Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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 of CWRU Cleveland Clinic  Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,11,22]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2015.1187"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/372773a0"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.1996.03890280098014"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1253"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0112073"},{"key":"e_1_2_6_7_1","first-page":"634","article-title":"Topical photodynamic therapy in dermatology","volume":"91","author":"Morton C. 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