{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:11:41Z","timestamp":1792192301052,"version":"4.4.0"},"reference-count":32,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Int J Surg Pathol"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    This study investigates the interplay between PD-L1, FOXP3+ regulatory T cells, and CD8+ cytotoxic T lymphocytes in penile squamous cell carcinoma (penile SCC), where understanding the tumor immune microenvironment is crucial.\n                    <jats:bold>Methods:<\/jats:bold>\n                    We analyzed 108 penile SCC specimens using tissue microarrays (528 spots). Immunohistochemistry was performed for PD-L1, FOXP3, and CD8. Expression was quantified in tumor and stromal compartments, and correlated with clinicopathological features including histological grade, HPV-associated morphology, and host inflammatory response.\n                    <jats:bold>Results:<\/jats:bold>\n                    PD-L1 in tumor cells positively correlated with intratumoral CD8+ (rho\u2009=\u20090.408,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u2009&lt;\u2009.001) and FOXP3+ T cells (rho\u2009=\u20090.293,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u2009=\u2009.009). Peritumoral FOXP3+ and CD8+ T cells also showed a strong correlation (rho\u2009=\u20090.753,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u2009&lt;\u2009.001). Higher PD-L1 and intratumoral CD8+ were associated with higher histological grade (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u2009&lt;\u2009.001). HPV-associated morphology correlated with higher PD-L1 (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u2009&lt;\u2009.001) but lower FOXP3+ infiltration (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u2009&lt;\u2009.001). Intense inflammatory response was associated with increased peritumoral FOXP3+ and CD8+ T cells (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    \u2009&lt;\u2009.001).\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    The immune microenvironment of penile SCC involves complex interactions among PD-L1, FOXP3+, and CD8+, and was significantly influenced by histological grade, HPV status, and inflammation. The strong co-localization of peritumoral regulatory and cytotoxic T cells suggests a critical regulatory axis. These findings highlight distinct immune profiles within penile SCC, offering insights for developing tailored immunotherapeutic strategies.\n                  <\/jats:p>","DOI":"10.1177\/10668969251361176","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T13:20:58Z","timestamp":1756992058000},"page":"73-79","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Interplay of PD-L1, FOXP3, and CD8 in the Immune Microenvironment of Penile Squamous Cell Carcinoma: Expression Profiles and Correlations"],"prefix":"10.1177","volume":"34","author":[{"given":"Sofia","family":"Canete-Portillo","sequence":"first","affiliation":[{"name":"Pathology Department, University of Alabama at Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3107-1429","authenticated-orcid":false,"given":"Antonio L.","family":"Cubilla","sequence":"additional","affiliation":[{"name":"Instituto de Patolog\u00eda e Investigaci\u00f3n, Asunci\u00f3n, Paraguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George J.","family":"Netto","sequence":"additional","affiliation":[{"name":"University of Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5824-9867","authenticated-orcid":false,"given":"Alcides","family":"Chaux","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Universidad del Norte, Asunci\u00f3n, Paraguay"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9103334"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00345-011-0802-0"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-021-02694-7"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01253"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.126462.1"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1055235"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0263895"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0300729"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2016.1269047"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.02894"},{"key":"e_1_3_2_12_2","first-page":"89","article-title":"Pancreatic cancer, methods and protocols","volume":"103","author":"Fedor HL","year":"2005","unstructured":"Fedor HL, Marzo AMD. 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