{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:28:42Z","timestamp":1792114122458,"version":"4.4.0"},"reference-count":51,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:00:00Z","timestamp":1740528000000},"content-version":"unspecified","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020M3A9G3080281"],"award-info":[{"award-number":["2020M3A9G3080281"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020M3A9G3080330"],"award-info":[{"award-number":["2020M3A9G3080330"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1A5A2031185"],"award-info":[{"award-number":["2020R1A5A2031185"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022R1A2C2009385"],"award-info":[{"award-number":["2022R1A2C2009385"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022R1A6A3A01086438"],"award-info":[{"award-number":["2022R1A6A3A01086438"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2024,12,30]]},"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The increased expression of programmed cell death ligand 1 (PD-L1) on a subset of immune cells in the peripheral blood has been frequently observed in patients with cancer, suggesting a relationship with PD-L1 expression in tumor tissues. In this study, we investigated the mechanisms underlying PD-L1 expression on various types of immune cells in the peripheral blood of patients with cancer.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>PD-L1 expression on various immune cell populations was analyzed in peripheral blood mononuclear cells of 112 patients with non-small cell lung cancer (NSCLC) using flow cytometry. A mouse model of X-ray-induced acute thrombocytopenia was used to investigate the relationship between thrombopoiesis and PD-L1-expressing platelet generation. The clinical significance of PD-L1-expressing platelets was analyzed in a cohort of patients with stage IV NSCLC who received a combination of anti-programmed cell death 1 (PD-1) therapy and chemotherapy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>All immune cell populations, including monocytes, T cells, B cells, and NK cells, showed higher PD-L1 expression in patients with cancer than in healthy controls. However, this increased frequency of PD-L1-expressing cells was not attributed to the expression of the cells themselves. Instead, it was entirely dependent on the direct interaction of the cells with PD-L1-expressing platelets. Notably, the platelet-dependent acquisition of PD-L1 on circulating immune cells of patients with lung cancer was observed in various other cancer types and was mechanistically associated with a surge in thrombopoiesis, resulting in the increased production of PD-L1-expressing reticulated platelets. Clinically, patients with enhanced thrombopoiesis and concurrently high PD-L1-expressing platelets exhibited a better response to anti-PD-1 therapy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These findings highlight the role of tumor-associated thrombopoiesis in generating PD-L1-expressing platelets that may serve as a resource for PD-L1-positive cells in the circulation and act as a predictive biomarker for anti-PD-1\/PD-L1 therapy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2024-010193","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T12:53:41Z","timestamp":1740574421000},"page":"e010193","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Enhanced thrombopoiesis supplies PD-L1 to circulating immune cells via the generation of PD-L1-expressing platelets in patients with lung cancer"],"prefix":"10.1136","volume":"13","author":[{"given":"Sung-Woo","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Chonnam National University Medical School, Hwasun-eup, Hwasun-gun, Jeollanam-do, Korea (the Republic of)"},{"name":"Medical Research Center for Combinatorial Tumor Immunotherapy, Chonnam National University Medical School, Hwasun-eup, Hwasun-gun, Jeollanam-do, Korea (the Republic of)"},{"name":"National Immunotherapy Innovation Center, Chonnam National University Medical School, Hwasun-eup, Hwasun-gun, Jeollanam-do, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saei","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Chonnam National University Medical School, Hwasun-eup, Hwasun-gun, Jeollanam-do, Korea (the Republic of)"},{"name":"Medical Research Center for Combinatorial Tumor Immunotherapy, Chonnam National University Medical School, Hwasun-eup, Hwasun-gun, Jeollanam-do, Korea (the Republic of)"},{"name":"National Immunotherapy Innovation Center, Chonnam National University Medical School, Hwasun-eup, Hwasun-gun, Jeollanam-do, Korea (the Republic of)"},{"name":"BioMedical Sciences Graduate Program, Chonnam National University Medical School, Hwasun-eup, Hwasun-gun, Jeollanam-do, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Ju","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Chonnam National University Medical School, Hwasun-eup, Hwasun-gun, Jeollanam-do, Korea (the Republic of)"},{"name":"Medical Research Center for Combinatorial Tumor Immunotherapy, Chonnam National University Medical School, Hwasun-eup, Hwasun-gun, Jeollanam-do, Korea (the Republic of)"},{"name":"National Immunotherapy Innovation Center, Chonnam National University Medical School, Hwasun-eup, Hwasun-gun, Jeollanam-do, Korea (the Republic of)"},{"name":"BioMedical Sciences Graduate Program, Chonnam National University Medical School, Hwasun-eup, Hwasun-gun, Jeollanam-do, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Eun","family":"Noh","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Chonnam National University Medical School, Hwasun-eup, Hwasun-gun, Jeollanam-do, Korea (the Republic of)"},{"name":"Medical Research Center for Combinatorial Tumor Immunotherapy, Chonnam National University Medical School, Hwasun-eup, Hwasun-gun, Jeollanam-do, Korea (the Republic of)"},{"name":"National Immunotherapy Innovation Center, Chonnam National University Medical School, Hwasun-eup, Hwasun-gun, Jeollanam-do, Korea (the Republic of)"},{"name":"BioMedical Sciences Graduate Program, Chonnam National University Medical School, Hwasun-eup, Hwasun-gun, Jeollanam-do, Korea (the Republic 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