{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:00:07Z","timestamp":1790125207088,"version":"4.0.1"},"reference-count":33,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"unspecified","delay-in-days":13,"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":["82372927"],"award-info":[{"award-number":["82372927"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82573174"],"award-info":[{"award-number":["82573174"]}],"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":[[2026,7,6]]},"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Metabolites sculpt the immunosuppressive tumor microenvironment (TME) that facilitates immune evasion. As a crucial signaling lysophospholipid, lysophosphatidylserine (LysoPS) correlates with advanced disease stages in multiple tumor types. However, the mechanisms by which LysoPS drives gastric cancer peritoneal metastasis remain undefined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Single-cell transcriptomic profiling of primary tumors, normal peritoneum, and metastatic lesions delineated mechanisms underlying LysoPS-mediated tumor-associated macrophages (TAMs) reprogramming. Immunohistochemistry and multiplex immunofluorescence validated GPR34-high TAMs infiltration in peritoneal metastases. Functional validation was performed using molecular assays and in vivo models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>LysoPS accumulated in ascites from patients with gastric cancer peritoneal metastasis, establishing an immunosuppressive TME that drove malignant progression. Using single-cell transcriptome sequencing, we identified a distinct subset of TAMs highly expressing GPR34 enriched in gastric cancer peritoneal metastases, which correlates with tumor progression and immune evasion. Mechanistically, LysoPS engagement of GPR34 activated ERK\/c-Jun signaling, transcriptionally upregulating AXL and CD36 to enhance efferocytosis. This effect drove TAMs toward an immunosuppressive phenotype, characterized by enhanced interleukin-10 and transforming growth factor-\u03b2 secretion. GPR34 inhibitor attenuated M2-like TAMs infiltration while bolstering cytotoxic T cells recruitment and curtailing programmed cell death protein 1 (PD-1)+T cells accumulation. Furthermore, combination with anti-PD-1 therapy synergistically suppressed tumor growth beyond monotherapy efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>LysoPS-GPR34 axis synergized with efferocytosis to amplify TAMs immunosuppressive properties, fostering an immune-evasive microenvironment; GPR34 inhibitor thus represents a promising strategy to potentiate PD-1 blockade efficacy in gastric cancer peritoneal metastasis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2026-015464","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T13:15:11Z","timestamp":1784034911000},"page":"e015464","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["LysoPS-GPR34 axis enhances tumor-associated macrophages efferocytosis to promote immune escape in gastric cancer peritoneal metastasis"],"prefix":"10.1136","volume":"14","author":[{"given":"Jialong","family":"Lv","sequence":"first","affiliation":[{"name":"Department of Colorectal Surgery, Huazhong University of Science and Technology Tongji Medical College Union Hospital, Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Huazhong University of Science and Technology Tongji Medical College Union Hospital, Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Huazhong University of Science and Technology Tongji Medical College Union Hospital, Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Colorectal 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