{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T13:57:55Z","timestamp":1780495075441,"version":"3.54.1"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T00:00:00Z","timestamp":1735257600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,1]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Activin A, a noteworthy member of the TGF\u2010\u03b2 superfamily. Activin A can regulate the biological functions of various immune cells, such as macrophages, neutrophils, NK cells, etc. The purpose of this study is to investigate the regulatory effect and related mechanisms of activin A on CD8\n +<\/jats:sup>\n T cells.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This study established a mouse subcutaneous transplantation model of hepatoma to explore whether activin A has a regulatory effect of CD8\n +<\/jats:sup>\n T cells. And reveal the biological characteristics of ActRIIA high CD8\n +<\/jats:sup>\n T cells.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We discovered that CD8\n +<\/jats:sup>\n T cells express ActRIIA, ActRIIB, and Smad2,3,4. Unlike high\u2010dose activin A, low\u2010dose activin A increased the content of CD8\n +<\/jats:sup>\n T cells while also suppressing tumor growth. In addition, low\u2010dose activin A promoted expression of perforin, granzyme B, CD69, CD11c, CD49b, Ki67 and ActRIIA in CD8\n +<\/jats:sup>\n T cells. And the results indicated that high\u2010dose activin A promotes the expression of PPM1A in T cells, while low\u2010dose activin A has no effect on these cells. The tumor contained more ActRIIA high CD8\n +<\/jats:sup>\n T cells compared to the peripheral blood and spleen. ActRIIA high CD8\n +<\/jats:sup>\n T cells highly express cytotoxic molecules and cytokines. And ActRIIA high CD8\n +<\/jats:sup>\n T cells not only expressed high levels of activation\/co\u2010stimulatory markers CD69, CD278, and CD28, but also high levels of inhibitory markers CD366 and KLRG1. Different chemokine receptors displayed varying levels of expression in ActRIIA high CD8\n +<\/jats:sup>\n T cells. Additionally, these cells have a high proliferative potential. Finally, overexpression of Mettl3 inhibited the expression of ActRIIA in CD8\n +<\/jats:sup>\n T cells.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n This study demonstrated that low\u2010dose activin A enhanced the anti\u2010tumor effect of CD8\n +<\/jats:sup>\n T cells, and ActRIIA high CD8\n +<\/jats:sup>\n T cells actively contribute to tumor immunity.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/cam4.70147","type":"journal-article","created":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T05:52:18Z","timestamp":1735278738000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Activin A promoted the anti\u2010tumor effect of\n \n ActRIIA\n high<\/sup>\n CD8\n <\/scp>\n +<\/sup>\n T cells in mouse hepatoma"],"prefix":"10.1002","volume":"14","author":[{"given":"Liangchang","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Oncology Affiliated Hospital of Shandong Second Medical University Weifang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Medical Laboratory Shandong Second Medical University Weifang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuguang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Affiliated Hospital of Shandong Second Medical University Weifang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7133-3644","authenticated-orcid":false,"given":"Chunhui","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Affiliated Hospital of Shandong Second Medical University Weifang China"},{"name":"Clinical Research Center Affiliated Hospital of Shandong Second Medical University Weifang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,27]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10082070"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00002.2018"},{"issue":"132","key":"e_1_2_13_4_1","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.mce.2004.07.011","article-title":"Activin: an important regulator of wound repair, fibrosis, and neuroprotection","volume":"225","author":"Ulyok S","year":"2004","journal-title":"Mol Cell Endocrinol"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a022137"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.14.1699"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2019.102314"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2015.118"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10010037"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570162043485077"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21804-1"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-004533"},{"issue":"6","key":"e_1_2_13_13_1","first-page":"2125","article-title":"Serum immunoreactive activin a levels in normal subjects and patients with various diseases","volume":"81","author":"Harada K","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-019-0814-7"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/resp.12937"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.12.010"},{"issue":"1","key":"e_1_2_13_17_1","first-page":"89","article-title":"Activin a promotes regulatory T\u2010cell\u2010mediated immunosuppression in irradiated breast cancer. 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