{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T18:15:38Z","timestamp":1793297738055,"version":"4.5.0"},"reference-count":19,"publisher":"BMJ","issue":"12","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"unspecified","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,11,17]]},"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:p>\n                    Common lymphatic endothelial and vascular endothelial receptor-1 (CLEVER-1) is a multifunctional scavenger receptor expressed on tumor-associated macrophages (TAMs). In a recent study published in the\n                    <jats:italic>Journal for ImmunoTherapy of Cancer<\/jats:italic>\n                    , Yu\n                    <jats:italic>et al<\/jats:italic>\n                    reported that CLEVER-1\n                    <jats:sup>+<\/jats:sup>\n                    TAMs accumulate in advanced gastric cancer (GC), associate with poor prognosis, and contribute to resistance to chemoimmunotherapy. CLEVER-1 blockade using bexmarilimab reprogrammed TAMs toward a pro-inflammatory phenotype by suppressing peroxisome proliferator-activated receptor gamma (PPAR\u03b3)-driven lipid metabolism and enhancing antigen presentation and inflammatory cytokine secretion. CLEVER-1 blockade also synergized with anti-programmed cell death protein 1 (PD-1) therapy in ex vivo GC models, particularly in tumors enriched with CLEVER-1\n                    <jats:sup>+<\/jats:sup>\n                    TAM. These findings identify CLEVER-1\n                    <jats:sup>+<\/jats:sup>\n                    TAMs as both biomarker and functional mediator of anti-PD-1 therapy resistance, providing a rationale for combining bexmarilimab with immune checkpoint blockade in GC. In this commentary, we discuss the mechanistic significance, translational potential, and clinical prospects of CLEVER-1 blockade to overcome immunotherapy resistance in GC.\n                  <\/jats:p>","DOI":"10.1136\/jitc-2025-013145","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T18:25:44Z","timestamp":1764786344000},"page":"e013145","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["CLEVER-1 blockade reprograms TAMs to overcome anti-PD-1 resistance in gastric cancer"],"prefix":"10.1136","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct03733990","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05428969","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05171062","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8744-6819","authenticated-orcid":false,"given":"Xiaonan","family":"Xiang","sequence":"first","affiliation":[{"name":"Department of Colorectal Surgery, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, China"},{"name":"Provincial Key Laboratory of Precise Diagnosis and Treatment of Abdominal Infection, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Zhejiang University School of 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