{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T03:41:46Z","timestamp":1789616506611,"version":"build-2803163510"},"reference-count":10,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"unspecified","delay-in-days":22,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82503827"],"award-info":[{"award-number":["82503827"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,6,8]]},"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:p>Retlirafusp alfa (SHR-1701), a bifunctional programmed death-ligand 1 (PD-L1) antibody fused to a TGF-\u03b2 trap, was approved in China on January 7, 2026 for first-line treatment of PD-L1-positive advanced gastric or gastroesophageal junction adenocarcinoma with chemotherapy. This first-in-class milestone revisits a key question raised by bintrafusp alfa (M7824): why can dual PD-L1\/TGF-\u03b2 targeting be active in selected settings yet inconsistent across tumors? We highlight that TGF-\u03b2-driven immune suppression and immune exclusion are often spatially organized within stromal niches, vary across indications, and are not always the dominant barrier even when PD-L1 is expressed. SHR-1701\u2019s approval provides proof of principle in a defined context and supports mechanism-aligned development using biomarker-driven selection, rational combinations and sequencing, and pharmacodynamic endpoints that directly test these assumptions.<\/jats:p>","DOI":"10.1136\/jitc-2026-015270","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:55:20Z","timestamp":1782237320000},"page":"e015270","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["From M7824 to SHR-1701: lessons for dual PD-L1\/TGF-\u03b2 targeting"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct04950322","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Ming","family":"Yi","sequence":"first","affiliation":[{"name":"Department of Breast Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China"},{"name":"Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianye","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gynecology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2499-1032","authenticated-orcid":false,"given":"Kongming","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijun","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Breast Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"2026062310551582000_14.6.e015270.1","unstructured":"National Medical Products Administration (NMPA) . 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