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Biomarkers that predict outcomes after BCG are lacking. The antitumor effects of BCG are driven by a cytotoxic T cell response, which may be controlled by immune checkpoint proteins like Programmed Death Ligand 1 (PD-L1). Here,\u00a0we hypothesized that PD-L1 protein expression could serve as a biomarker for BCG-failure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>HR-NMIBC patients who received\u2009\u2265\u20095 BCG instillations were included. Tissue microarrays were constructed from BCG-na\u00efve tumors and recurrences and stained with the PD-L1 (SP142) antibody. PD-L1 status was defined as\u2009\u2265\u20095% tumor-infiltrating immune cells with membrane staining in the tumor area. Clinicopathological associations with PD-L1 positive tumors\u00a0were investigated, and time-to-event analyses were performed comparing PD-L1 positive vs. negative tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      432 BCG-na\u00efve tumors and 160 recurrences were included, and 91% of patients received adequate BCG. In BCG-na\u00efve tumors, PD-L1 was expressed in 7% of patients and PD-L1 expression was associated with stage T1 versus Ta disease (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.015). PD-L1 expression was not associated with treatment failure after adequate BCG (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.782) nor with progression-free survival (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.732). Testing cut-offs of\u2009\u2265\u20091% and\u2009\u2265\u200910% PD-L1 positivity did not alter results. High PD-L1 expression was more frequent in tumor recurrences (14%) as compared to BCG-na\u00efve tumors (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.012).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PD-L1 expression in HR-NMIBC is not a biomarker of response to BCG. However, PD-L1 is higher in a subset of tumors that failed BCG treatment. More research is needed to determine the role of PD-L1 in tumors where BCG treatment failed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00345-024-05392-5","type":"journal-article","created":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T07:17:27Z","timestamp":1735888647000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["PD-L1 expression in high-risk non-muscle invasive bladder cancer is not a biomarker of response to BCG"],"prefix":"10.1007","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6853-5982","authenticated-orcid":false,"given":"Florus C.","family":"de Jong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vebj\u00f8rn","family":"Kvikstad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert F.","family":"Hoedemaeker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelique C. 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