{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:00:36Z","timestamp":1790834436371,"version":"4.1.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cadonilimab is a PD\u20101\/CTLA\u20104 bispecific antibody with robust activity in platinum\u2010pretreated advanced cervical cancer, while its first\u2010line value and resistance mechanisms remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multicenter retrospective study enrolled 52 treatment\u2010naive patients with recurrent\/metastatic cervical cancer (R\/M CC) receiving cadonilimab plus chemotherapy. We assessed clinical efficacy and safety, and performed RNA\u2010seq and immunohistochemistry for exploratory biomarker analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The 2\u2010year overall survival, 2\u2010year progression\u2010free survival and objective response rate were 82.6%, 66.7% and 75.0%, respectively. Main treatment\u2010related adverse events included myelosuppression, thyroid dysfunction, gastrointestinal reactions and fatigue, demonstrating acceptable safety. Transcriptomic data showed suppressed Hippo, NF\u2010\u03baB, RIG\u20101 pathways and reduced M1\u2010macrophage polarization in patients with longer PFS. Candidate genes including GGT6 and FRG2 were identified as putative resistance\u2010associated markers in this small exploratory cohort. Higher M1\u2010macrophage polarization and p\u2010STAT1 expression were observed in short\u2010PFS patients, indicating a possible link between p\u2010STAT1 activation and M1\u2010macrophage enrichment. Of note, outcomes should be interpreted considering the retrospective single\u2010arm design and limited sample size.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Cadonilimab\u2010containing regimen achieved promising efficacy and an acceptable safety profile as first\u2010line therapy for R\/M CC. The biomarker findings are exploratory and provide preliminary evidence for future research on bispecific\u2010antibody resistance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1967065","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:42:37Z","timestamp":1790833357000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Anti\u2010PD\u20101\/CTLA\u20104 bispecific antibody\u2010based combination therapy for cervical cancer: a multicenter study with biomarker analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiwei","family":"Li","sequence":"first","affiliation":[{"name":"Department of Oncology, The Second Xiangya Hospital, Central South University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Changde Hospital, Xiangya School of Medicine","place":["Changde, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Second Xiangya Hospital, Central South University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Second Xiangya Hospital, Central South University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of 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