{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:22:27Z","timestamp":1787772147818,"version":"build-2784847793"},"reference-count":35,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"unspecified","delay-in-days":26,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2022M710760"],"award-info":[{"award-number":["2022M710760"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024T170164"],"award-info":[{"award-number":["2024T170164"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82202874"],"award-info":[{"award-number":["82202874"]}],"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":["82203567"],"award-info":[{"award-number":["82203567"]}],"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":["82573627"],"award-info":[{"award-number":["82573627"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Yangfan Project of Shanghai","award":["22YF1431800"],"award-info":[{"award-number":["22YF1431800"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,1,13]]},"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hepatocellular carcinoma (HCC) is a global health challenge with high mortality rates, particularly in patients with advanced disease and lung metastasis. T-cell receptor (TCR)-T cell therapy based on specific neoantigens, is an emerging treatment with potential for HCC. However, the prognosis of patients remains poor, underscoring the need for novel targets and strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a comprehensive study to investigate the role of\n                      <jats:italic>C7orf50<\/jats:italic>\n                      and its neoantigens in HCC. We evaluated the functional impact on HCC progression and metastasis\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      , and further explored the mechanism by which\n                      <jats:italic>C7orf50<\/jats:italic>\n                      promotes cancer metastasis and remodels tumor immune environment. Using exome and transcriptome sequencing, we identified neoantigens associated with\n                      <jats:italic>C7orf50<\/jats:italic>\n                      and assessed their potential in TCR-T therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments revealed that\n                      <jats:italic>C7orf50<\/jats:italic>\n                      overexpression enhances HCC cell proliferation, migration, and invasion, while knockdown inhibits these processes.\n                      <jats:italic>In vivo<\/jats:italic>\n                      ,\n                      <jats:italic>C7orf50<\/jats:italic>\n                      promoted tumor growth and lung metastasis, with a significant correlation between\n                      <jats:italic>C7orf50<\/jats:italic>\n                      expression and poor clinical outcomes in patients with HCC. We further demonstrated that C7orf50 activates the NF-\u03baB\/PAI-1 pathway by binding to AEG-1 and facilitating its nuclear translocation, thereby promoting tumor-associated macrophage recruitment. Meanwhile, we found that TCR-T from\n                      <jats:italic>C7orf50<\/jats:italic>\n                      -related neoantigen could obviously realize the killing effect on HCC cells, revealing its great role in cell therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>C7orf50<\/jats:italic>\n                      is a critical mediator of HCC progression and lung metastasis, acting through the NF-\u03baB\/PAI-1 pathway and AEG-1. Its expression levels, along with those of PAI-1 and CD68, serve as independent prognostic markers. And\n                      <jats:italic>C7orf50<\/jats:italic>\n                      -related neoantigen shows great application potential in TCR-T therapy. These findings provide a foundation for developing\n                      <jats:italic>C7orf50<\/jats:italic>\n                      -targeted therapies and highlight its potential in precision medicine and immunotherapy for HCC.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-011997","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T15:40:26Z","timestamp":1769528426000},"page":"e011997","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Tumor neoantigen gene C7orf50 remodels the immune microenvironment by recruiting tumor-associated macrophages to promote hepatocellular carcinoma progression and lung metastasis"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct03132792","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02932956","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6312-3366","authenticated-orcid":false,"given":"Jia","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Cancer Invasion, Zhongshan Hospital Fudan University, Shanghai, China"},{"name":"Department of Thoracic Surgery, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1023-8090","authenticated-orcid":false,"given":"Xinming","family":"Ye","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Cancer Invasion, Zhongshan Hospital Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Su","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Cancer Invasion, Zhongshan Hospital Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Cancer Invasion, Zhongshan Hospital Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5396-3204","authenticated-orcid":false,"given":"Changzhou","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Cancer Invasion, Zhongshan Hospital Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Gong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Cancer 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