{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T09:07:46Z","timestamp":1780304866225,"version":"3.54.0"},"reference-count":26,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA204158"],"award-info":[{"award-number":["R01 CA204158"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 CA084203"],"award-info":[{"award-number":["P01 CA084203"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cutan Pathol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Basal cell carcinomas (BCCs) are thought to reside within an immunosuppressed tumor microenvironment, but a detailed characterization of BCC\u2010associated immune cells was lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Utilizing multiplex immunohistochemistry (IHC) (Vectra Polaris, Akoya Biosciences), we designed two staining panels, targeting either T cells (CD3, CD4, CD8, FoxP3, PD1) or myeloid cells (neutrophil elastase, CD68, CD163, HLADR, CD1c). Formalin\u2010fixed paraffin\u2010embedded (FFPE) BCC tumor specimens (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200930) were analyzed using the panels. The majority of immune cells reside at the peritumoral margin; therefore, a boundary zone of 150\u2009\u03bcm around tumor nests was used to capture them.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A CD8\/T\u2010reg ratio and M1\/M2 macrophage ratio of &lt;\u20090.5 was observed across all BCC specimens, confirming an overall immunosuppressive phenotype. Among different histologic subtypes, infiltrative BCC had significantly lower CD8 T cells (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.038), T\u2010regulatory cells (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.039), and CD8\/T\u2010reg ratio (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.048), as well as lower M1\/M2 ratio (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.034) compared to non\u2010infiltrative BCC subtypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The association of infiltrative BCC with a more immunosuppressed microenvironment may contribute to more aggressive biological behavior. Overall, these data demonstrate a method to determine T cell and myeloid profiles in fixed FFPE skin tumor tissues that can identify subtle immune profile differences.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cup.70098","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:31:09Z","timestamp":1775003469000},"page":"624-632","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multiplexed Immunofluorescent Characterization of\n                    <scp>T<\/scp>\n                    \u2010Cell and Myeloid Cell Populations Reveals Histologic Subtype Differences Within the Immunosuppressive Landscape of Human Basal Cell Carcinoma"],"prefix":"10.1111","volume":"53","author":[{"given":"Alan S.","family":"Shen","sequence":"first","affiliation":[{"name":"Cleveland Clinic Lerner College of Medicine of Case Western Reserve University  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren E.","family":"Heusinkveld","sequence":"additional","affiliation":[{"name":"Department of Pathology Mass General Brigham, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Zalavadia","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Lerner Research Institute Imaging Core  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrelie","family":"Branicky","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Lerner Research Institute Imaging Core  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1893-8561","authenticated-orcid":false,"given":"Sanjay","family":"Anand","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Lerner College of Medicine of Case Western Reserve University  Cleveland Ohio USA"},{"name":"Department of Biomedical Engineering Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Piliang","sequence":"additional","affiliation":[{"name":"Department of Pathology Cleveland Clinic  Cleveland Ohio USA"},{"name":"Department of Dermatology Cleveland Clinic  Cleveland Ohio 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":"Cleveland Clinic Lerner College of Medicine of Case Western Reserve University  Cleveland Ohio USA"},{"name":"Department of Biomedical Engineering Cleveland Clinic  Cleveland Ohio USA"},{"name":"Department of Dermatology Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpt.2024.08.002"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2018.03.060"},{"issue":"3","key":"e_1_2_11_4_1","article-title":"Aggressive Basal Cell Carcinoma: Dermatoscopy Vascular Features as Clues to the Diagnosis","volume":"2","author":"Pyne J.","year":"2012","journal-title":"Dermatology Practical & Conceptual"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ad.2022.01.026"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000372-200608000-00002"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15092453"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.5021\/ad.22.042"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700884"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijd.15065"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-2440"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-021-02089-2"},{"issue":"10","key":"e_1_2_11_13_1","article-title":"Local Immune Response in Cutaneous Basal Cell Carcinoma","volume":"64","author":"Omland S. 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