{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T16:23:33Z","timestamp":1783441413949,"version":"3.54.6"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Papillary thyroid cancer (PTC) is the most common thyroid malignancy. Based on single-cell RNA sequencing, a previously unrecognized CD4+ T cell subset was identified, termed EGR1+CD4+ T cells. This subset produced high levels of IL-10 and IFN-\u03b3 in response to phorbol 12-myristate 13-acetate (PMA) and ionomycin, and showed distinct molecular pathway activity compared to CD4+ Tregs. CD4+ T cell-specific overexpression of EGR1 in vitro enhanced tumor cell proliferation, invasion, and migration when co-cultured with PTC cell lines. The expression profiling analysis of immune checkpoint molecules indicated that CD96 was commonly up-regulated in EGR1+CD4+ T cells, CD4+ Tregs, and other T cell subsets, especially in tumor tissues. Single CD96 blockade significantly increased the levels of IFN-\u03b3, IL-17a, and IL-10 in EGR1+CD4+ T cells and inhibited the proliferation of PTC tumor cells. Co-blockade of CD96\/TIGIT significantly enhanced the production of IFN-\u03b3, TNF-\u03b1, and IL-17a in both EGR1+CD4+ T cells and CD3+CD4+ T cells, which also suppressed cell proliferation, invasion, and migration when co-cultured with PTC tumor cells. These findings indicated that EGR1+CD4+ T cells were a novel CD4+ T cell subset with specific functions. Single CD96 blockade or co-blockade of CD96\/TIGIT enhanced antitumor immunity of EGR1+CD4+ T cells, which might be promising therapeutic strategies in PTC treatment.<\/jats:p>","DOI":"10.1093\/gpbjnl\/qzag060","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T15:46:59Z","timestamp":1783439219000},"source":"Crossref","is-referenced-by-count":0,"title":["Single-cell RNA Sequencing Reveals A Tumor-Promoting Role of EGR1+CD4+ T Cells in Papillary Thyroid Cancer"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0659-3575","authenticated-orcid":false,"given":"Zhengshi","family":"Wang","sequence":"first","affiliation":[{"name":"Tongji University Department of Breast and Thyroid Surgery, Shanghai Tenth People\u2019s Hospital, School of Medicine, , Shanghai 200072,","place":["China"]},{"name":"Tongji University Shanghai Center for Thyroid Diseases, Shanghai Tenth People\u2019s Hospital, School of Medicine, , Shanghai 200072,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9559-2787","authenticated-orcid":false,"given":"Yun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tongji University Department of Breast and Thyroid Surgery, Shanghai Tenth People\u2019s Hospital, School of Medicine, , Shanghai 200072,","place":["China"]},{"name":"Tongji University Shanghai Center for Thyroid Diseases, Shanghai Tenth People\u2019s Hospital, School of Medicine, , Shanghai 200072,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9056-5317","authenticated-orcid":false,"given":"Yong","family":"Xu","sequence":"additional","affiliation":[{"name":"Hunan Normal University Department of Laboratory, Yueyang Hospital, , Yueyang 414000,","place":["China"]},{"name":"Hunan Normal University Medical School Department of Immunology, , Changsha 410013,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4872-7841","authenticated-orcid":false,"given":"Zhaohui","family":"Liu","sequence":"additional","affiliation":[{"name":"Hunan Normal University Breast and Thyroid Surgery, Yueyang Hospital, , Yueyang 414000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2625-2703","authenticated-orcid":false,"given":"Shengyun","family":"Wang","sequence":"additional","affiliation":[{"name":"Naval Medical University Department of Emergency and Critical Care Medicine, Changzheng Hospital, , Shanghai 200003,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5249-918X","authenticated-orcid":false,"given":"Zhiqiang","family":"Yin","sequence":"additional","affiliation":[{"name":"Tongji University Department of Breast and Thyroid Surgery, Shanghai Tenth People\u2019s Hospital, School of Medicine, , Shanghai 200072,","place":["China"]},{"name":"Tongji University Shanghai Center for Thyroid Diseases, Shanghai Tenth People\u2019s Hospital, School of Medicine, , Shanghai 200072,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7706-8308","authenticated-orcid":false,"given":"Youlutuziayi","family":"Rixiati","sequence":"additional","affiliation":[{"name":"Fudan University Huashan Hospital Department of Pathology, , Shanghai 200040,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,7]]},"container-title":["Genomics, Proteomics &amp; Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/gpb\/advance-article-pdf\/doi\/10.1093\/gpbjnl\/qzag060\/68709068\/qzag060.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/gpb\/advance-article-pdf\/doi\/10.1093\/gpbjnl\/qzag060\/68709068\/qzag060.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T15:46:59Z","timestamp":1783439219000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/gpb\/advance-article\/doi\/10.1093\/gpbjnl\/qzag060\/8726275"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,7]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/gpbjnl\/qzag060","relation":{},"ISSN":["1672-0229","2210-3244"],"issn-type":[{"value":"1672-0229","type":"print"},{"value":"2210-3244","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,7]]},"article-number":"qzag060"}}