{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:04:49Z","timestamp":1788271489470,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T00:00:00Z","timestamp":1699228800000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Immune checkpoint inhibitor (ICI) combination therapies have shown promise in the first\u2010line treatment of advanced biliary tract cancer (BTC). However, the best partner remains to be validated. Moreover, progress on biomarkers predicting the efficacy of ICI in BTC is slow. This study aimed to assess the efficacy and investigate reliable predictive biomarkers of programmed cell death protein\u20101 (PD\u20101) antibody combination therapy in the first\u2010line treatment of advanced BTC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical data from patients with advanced BTC who received chemotherapy or anti\u2010PD\u20101 combination therapy as first\u2010line were collected. The primary outcome was overall survival (OS). Biomarkers, including peripheral blood inflammation scores, genetic alterations, and tumor microenvironment were investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Findings<\/jats:title><jats:p>Sixty\u2010four patients were recruited and divided into four treatment groups: chemotherapy, anti\u2010PD\u20101 plus chemotherapy, anti\u2010PD\u20101 plus targeted therapy, and triple group (anti\u2010PD\u20101 plus chemotherapy and targeted therapy). The median OS was 7.9, 11.3, 12.8, and 28.7\u2009months, respectively. Compared to chemotherapy, mOS significantly prolonged in the triple group (<jats:italic>p<\/jats:italic>\u2009=\u20090.031). It showed that patients with five different peripheral blood inflammation scores had significantly prolonged mOS (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Genetic testing results suggested that patients with poor survival all had <jats:italic>TP53<\/jats:italic> mutations and higher levels of <jats:italic>KRAS<\/jats:italic> and <jats:italic>ERBB2<\/jats:italic> mutations. Low FOXP3\/CD8 ratio was associated with prolonged OS (<jats:italic>p<\/jats:italic>\u2009=\u20090.029). With CD4\u2010low, CD8\u2010high, CD56\u2010positive, CD163\u2010high, FOXP3\u2010high and MPO\u2010high in TME as one factor, we calculated PLUS score according to the number of factors. The high\u2010PLUS (&gt;2) group showed significantly superior OS (<jats:italic>p<\/jats:italic>\u2009=\u20090.003).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>First\u2010line anti\u2010PD\u20101 combination therapy was superior to chemotherapy, and triple therapy significantly improved survival. Peripheral blood immune\u2010inflammation score, FOXP3\/CD8 ratio, and PLUS have potential as biomarkers for predicting the efficacy of first\u2010line anti\u2010PD\u20101 therapy in advanced BTC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.6628","type":"journal-article","created":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T13:57:50Z","timestamp":1699279070000},"page":"20699-20711","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Survival benefit and biomarker of PD\u20101 inhibitor combination therapy in first\u2010line of advanced biliary tract cancer: A retrospective study"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0215-2895","authenticated-orcid":false,"given":"Jingyi","family":"Guo","sequence":"first","affiliation":[{"name":"The Comprehensive Cancer Centre, Department of Oncology, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical 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Department of Oncology, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School  Nanjing China"},{"name":"Department of Oncology China Pharmaceutical University Nanjing Drum Tower Hospital  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oncology Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine  Nanjing China"},{"name":"Department of Pathology, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yudong","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Hepatopancreatobiliary Surgery, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School  Nanjing 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