{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T17:46:11Z","timestamp":1777139171971,"version":"3.51.4"},"reference-count":43,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T00:00:00Z","timestamp":1674172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273199"],"award-info":[{"award-number":["82273199"]}],"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":["81772779"],"award-info":[{"award-number":["81772779"]}],"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":["LGY2017068"],"award-info":[{"award-number":["LGY2017068"]}],"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":["2015-WSN-034"],"award-info":[{"award-number":["2015-WSN-034"]}],"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":["ZDRCA2016003"],"award-info":[{"award-number":["ZDRCA2016003"]}],"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":["ZDXKB2016005"],"award-info":[{"award-number":["ZDXKB2016005"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"\u201cProfessionals from Six-Pronged Top-Talent Program\u201d of Jiangsu Province","award":["82273199"],"award-info":[{"award-number":["82273199"]}]},{"name":"\u201cProfessionals from Six-Pronged Top-Talent Program\u201d of Jiangsu Province","award":["81772779"],"award-info":[{"award-number":["81772779"]}]},{"name":"\u201cProfessionals from Six-Pronged Top-Talent Program\u201d of Jiangsu Province","award":["LGY2017068"],"award-info":[{"award-number":["LGY2017068"]}]},{"name":"\u201cProfessionals from Six-Pronged Top-Talent Program\u201d of Jiangsu Province","award":["2015-WSN-034"],"award-info":[{"award-number":["2015-WSN-034"]}]},{"name":"\u201cProfessionals from Six-Pronged Top-Talent Program\u201d of Jiangsu Province","award":["ZDRCA2016003"],"award-info":[{"award-number":["ZDRCA2016003"]}]},{"name":"\u201cProfessionals from Six-Pronged Top-Talent Program\u201d of Jiangsu Province","award":["ZDXKB2016005"],"award-info":[{"award-number":["ZDXKB2016005"]}]},{"name":"\u201cThe Six Top Talent Project\u201d of Jiangsu Province","award":["82273199"],"award-info":[{"award-number":["82273199"]}]},{"name":"\u201cThe Six Top Talent Project\u201d of Jiangsu Province","award":["81772779"],"award-info":[{"award-number":["81772779"]}]},{"name":"\u201cThe Six Top Talent Project\u201d of Jiangsu Province","award":["LGY2017068"],"award-info":[{"award-number":["LGY2017068"]}]},{"name":"\u201cThe Six Top Talent Project\u201d of Jiangsu Province","award":["2015-WSN-034"],"award-info":[{"award-number":["2015-WSN-034"]}]},{"name":"\u201cThe Six Top Talent Project\u201d of Jiangsu Province","award":["ZDRCA2016003"],"award-info":[{"award-number":["ZDRCA2016003"]}]},{"name":"\u201cThe Six Top Talent Project\u201d of Jiangsu Province","award":["ZDXKB2016005"],"award-info":[{"award-number":["ZDXKB2016005"]}]},{"name":"Medical Talent of Empowering Medicine through Science and Education Program of Jiangsu Province","award":["82273199"],"award-info":[{"award-number":["82273199"]}]},{"name":"Medical Talent of Empowering Medicine through Science and Education Program of Jiangsu Province","award":["81772779"],"award-info":[{"award-number":["81772779"]}]},{"name":"Medical Talent of Empowering Medicine through Science and Education Program of Jiangsu Province","award":["LGY2017068"],"award-info":[{"award-number":["LGY2017068"]}]},{"name":"Medical Talent of Empowering Medicine through Science and Education Program of Jiangsu Province","award":["2015-WSN-034"],"award-info":[{"award-number":["2015-WSN-034"]}]},{"name":"Medical Talent of Empowering Medicine through Science and Education Program of Jiangsu Province","award":["ZDRCA2016003"],"award-info":[{"award-number":["ZDRCA2016003"]}]},{"name":"Medical Talent of Empowering Medicine through Science and Education Program of Jiangsu Province","award":["ZDXKB2016005"],"award-info":[{"award-number":["ZDXKB2016005"]}]},{"name":"Key Laboratory for Medicine of Jiangsu Province of China","award":["82273199"],"award-info":[{"award-number":["82273199"]}]},{"name":"Key Laboratory for Medicine of Jiangsu Province of China","award":["81772779"],"award-info":[{"award-number":["81772779"]}]},{"name":"Key Laboratory for Medicine of Jiangsu Province of China","award":["LGY2017068"],"award-info":[{"award-number":["LGY2017068"]}]},{"name":"Key Laboratory for Medicine of Jiangsu Province of China","award":["2015-WSN-034"],"award-info":[{"award-number":["2015-WSN-034"]}]},{"name":"Key Laboratory for Medicine of Jiangsu Province of China","award":["ZDRCA2016003"],"award-info":[{"award-number":["ZDRCA2016003"]}]},{"name":"Key Laboratory for Medicine of Jiangsu Province of China","award":["ZDXKB2016005"],"award-info":[{"award-number":["ZDXKB2016005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Regulatory T cells (Tregs) are usually enriched in ovarian cancer (OC), and their immunosuppressive function plays a key role in tumorigenesis and progression. We mainly explored the phenotypical characterization of Treg-related markers on \u03b1\u03b2 and \u03b3\u03b4 T cell subsets in patients with OC. Materials and Methods: Thirty-six untreated patients with OC at the Women\u2019s Hospital of Nanjing Medical University from September 2019 to August 2021 were enrolled. Phenotypical characterization of Tregs-related markers were detected by flow cytometry (FCM). Enzyme-linked immunosorbent assay was used to detect the levels of carbohydrate antigen (CA125) and transforming growth factor \u03b2 (TGF-\u03b2). The level of human epididymis protein 4 (HE4) was detected by electrochemiluminescence immunoassay. Results: Circulating CD4+ Tregs, CD8+ Tregs, and CD3+\u03b3\u03b4 T cell subpopulations from OC patients have elevated Foxp3, CD25, CD122, V\u03b41, and reduced CD28 expression compared to benign ovarian tumor (BOT) patients and healthy controls (HC). The upregulation of Foxp3 and V\u03b41 and the downregulation of CD28 were highly specific for maintaining the immunosuppression function of CD4+ Tregs, CD3+\u03b3\u03b4 T cells, and CD8+ Tregs in OC patients. These Treg subpopulations were able to discriminate OC from BOT and HC. The levels of CA125, HE4, and TGF-\u03b2 were increased in OC patients. A significant positive correlation between Treg subpopulations and CA125, HE4, and TGF-\u03b2 was revealed. Conclusions: Proportions of CD4+ Tregs, CD8+ Tregs, and CD3+\u03b3\u03b4 T cell subsets were significantly increased in OC patients and were positively correlated with FIGO stage\/metastasis status, CA125, HE4, and TGF-\u03b2. These indicators have the potential to be used as immunosurveillance biomarkers for OC.<\/jats:p>","DOI":"10.3390\/medicina59020205","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T02:43:29Z","timestamp":1674182609000},"page":"205","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Circulating CD4+ Treg, CD8+ Treg, and CD3+ \u03b3\u03b4 T Cell Subpopulations in Ovarian Cancer"],"prefix":"10.3390","volume":"59","author":[{"given":"Rong","family":"Li","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China"},{"name":"National Key Clinical Department of Laboratory Medicine, Nanjing 210029, China"},{"name":"Department of Gynecology, Women\u2019s Hospital of Nanjing Medical University, Nanjing 210004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The Affiliated Taizhou People\u2019s Hospital of Nanjing Medical University, Taizhou 225300, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6729-6788","authenticated-orcid":false,"given":"Ming","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Children\u2019s Hospital of Fudan University, National Children\u2019s Medical Center, Shanghai 201102, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuna","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China"},{"name":"National Key Clinical Department of Laboratory Medicine, Nanjing 210029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China"},{"name":"National Key Clinical Department of Laboratory Medicine, Nanjing 210029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenwen","family":"Shang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China"},{"name":"National Key Clinical Department of Laboratory Medicine, Nanjing 210029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China"},{"name":"National Key Clinical Department of Laboratory Medicine, Nanjing 210029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9323-4425","authenticated-orcid":false,"given":"Xuemei","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Women\u2019s Hospital of Nanjing Medical University, Nanjing 210004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China"},{"name":"National Key Clinical Department of Laboratory Medicine, Nanjing 210029, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,20]]},"reference":[{"key":"ref_1","first-page":"e30561","article-title":"Aetiology, Epidemiology, Histopathology, Classification, Detailed Evaluation, and Treatment of Ovarian Cancer","volume":"14","author":"Zamwar","year":"2022","journal-title":"Cureus"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1002\/ijc.34002","article-title":"Ovarian cancer today and tomorrow: A global assessment by world region and Human Development Index using GLOBOCAN 2020","volume":"151","author":"Cabasag","year":"2022","journal-title":"Int. J. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e936","DOI":"10.1002\/hsr2.936","article-title":"The global, regional and national epidemiology, incidence, mortality, and burden of ovarian cancer","volume":"5","author":"Mazidimoradi","year":"2022","journal-title":"Health Sci. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"284","DOI":"10.3322\/caac.21456","article-title":"Ovarian cancer statistics, 2018: Ovarian Cancer Statistics, 2018","volume":"68","author":"Torre","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_5","first-page":"92","article-title":"Peptide-based targeting of immunosuppressive cells in cancer","volume":"5","author":"Trac","year":"2020","journal-title":"Bioact. Mater."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.1111\/febs.13656","article-title":"Targeting regulatory T cells in tumors","volume":"283","author":"Liu","year":"2016","journal-title":"FEBS J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/j.immuni.2016.10.021","article-title":"Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells","volume":"45","author":"Arrigoni","year":"2016","journal-title":"Immunity"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"100926","DOI":"10.1016\/j.gore.2022.100926","article-title":"Understanding the impact of chemotherapy on the immune landscape of high-grade serous ovarian cancer","volume":"39","author":"Vanguri","year":"2022","journal-title":"Gynecol. Oncol. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1158\/1078-0432.CCR-16-1433","article-title":"Neoadjuvant Chemotherapy of Ovarian Cancer Results in Three Patterns of Tumor-Infiltrating Lymphocyte Response with Distinct Implications for Immunotherapy","volume":"23","author":"Lo","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2748","DOI":"10.1111\/j.1582-4934.2009.00911.x","article-title":"Ovarian cancer cytoreduction induces changes in T cell population subsets reducing immunosuppression","volume":"14","author":"Napoletano","year":"2010","journal-title":"J. Cell. Mol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"15179","DOI":"10.1038\/srep15179","article-title":"Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in cancers: A systematic review and meta-analysis","volume":"5","author":"Shang","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/cmi.2015.57","article-title":"Analysis of CD8+ Treg cells in patients with ovarian cancer: A possible mechanism for immune impairment","volume":"12","author":"Zhang","year":"2015","journal-title":"Cell. Mol. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.immuni.2009.03.019","article-title":"Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor","volume":"30","author":"Miyara","year":"2009","journal-title":"Immunity"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2965","DOI":"10.3389\/fimmu.2019.02965","article-title":"The Intriguing History of Cancer Immunotherapy","volume":"10","author":"Dobosz","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"654877","DOI":"10.3389\/fimmu.2021.654877","article-title":"The Cancer Cell Dissemination Machinery as an Immunosuppressive Niche: A New Obstacle Towards the Era of Cancer Immunotherapy","volume":"12","author":"Asiry","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_16","first-page":"2287","article-title":"Changes in tumor markers, coagulation function and serum VEGF in patients with ovarian cancer and benign ovarian disease","volume":"25","author":"Wang","year":"2020","journal-title":"J. BUON Off. J. Balk. Union Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"188503","DOI":"10.1016\/j.bbcan.2021.188503","article-title":"Roles of CA125 in diagnosis, prediction, and oncogenesis of ovarian cancer","volume":"1875","author":"Zhang","year":"2021","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1007\/s00404-020-05527-0","article-title":"The differential diagnostic value and clinical significance of serum HE4 in ovarian disease with elevated CA125","volume":"301","author":"Li","year":"2020","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1158\/2326-6066.CIR-16-0193","article-title":"Regulatory T Cells: Differentiation and Function","volume":"4","author":"Plitas","year":"2016","journal-title":"Cancer Immunol. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/s41571-019-0175-7","article-title":"Regulatory T cells in cancer immunosuppression\u2014Implications for anticancer therapy","volume":"16","author":"Togashi","year":"2019","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1038\/nm1093","article-title":"Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival","volume":"10","author":"Curiel","year":"2004","journal-title":"Nat. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41419-020-03272-5","article-title":"Glucose metabolism characteristics and TLR8-mediated metabolic control of CD4+ Treg cells in ovarian cancer cells microenvironment","volume":"12","author":"Xu","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1007\/s00262-015-1753-x","article-title":"Regulatory T cells, inherited variation, and clinical outcome in epithelial ovarian cancer","volume":"64","author":"Knutson","year":"2015","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1111\/j.1600-065X.2011.01018.x","article-title":"Regulatory T cells and Foxp3: Regulatory T cells and Foxp3","volume":"241","author":"Rudensky","year":"2011","journal-title":"Immunol. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4557","DOI":"10.1158\/0008-5472.CAN-18-3962","article-title":"The Tumor Microenvironment Innately Modulates Cancer Progression","volume":"79","author":"Hinshaw","year":"2019","journal-title":"Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/imm.12600","article-title":"Mouse and human CD8(+) CD28(low) regulatory T lymphocytes differentiate in the thymus","volume":"148","author":"Vuddamalay","year":"2016","journal-title":"Immunology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3389\/fimmu.2017.00031","article-title":"CD28- and CD28lowCD8+ Regulatory T Cells: Of Mice and Men","volume":"8","author":"Vuddamalay","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1002\/eji.200839210","article-title":"CD122+CD8+ Treg suppress vaccine-induced antitumor immune responses in lymphodepleted mice","volume":"40","author":"Wang","year":"2010","journal-title":"Eur. J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7093","DOI":"10.4049\/jimmunol.175.11.7093","article-title":"Cutting Edge: CD8 + CD122 + Regulatory T Cells Produce IL-10 to Suppress IFN-\u03b3 Production and Proliferation of CD8 + T Cells","volume":"175","author":"Endharti","year":"2005","journal-title":"J. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1038\/cmi.2018.170","article-title":"Immune regulation by CD8+ Treg cells: Novel possibilities for anticancer immunotherapy","volume":"15","author":"Zhang","year":"2018","journal-title":"Cell. Mol. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.cell.2018.12.040","article-title":"Commensal Microbiota Promote Lung Cancer Development via \u03b3\u03b4 T Cells","volume":"176","author":"Jin","year":"2019","journal-title":"Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nature14282","article-title":"IL-17-producing \u03b3\u03b4 T cells and neutrophils conspire to promote breast cancer metastasis","volume":"522","author":"Coffelt","year":"2015","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e1277305","DOI":"10.1080\/2162402X.2016.1277305","article-title":"Tumor-infiltrating CD39 + \u03b3 \u03b4 Tregs are novel immunosuppressive T cells in human colorectal cancer","volume":"6","author":"Hu","year":"2017","journal-title":"OncoImmunology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/s12967-019-1897-0","article-title":"Distribution and functions of \u03b3\u03b4 T cells infiltrated in the ovarian cancer microenvironment","volume":"17","author":"Chen","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"691","DOI":"10.3389\/fimmu.2019.00691","article-title":"Clinical Relevance and Immunosuppressive Pattern of Circulating and Infiltrating Subsets of Myeloid-Derived Suppressor Cells (MDSCs) in Epithelial Ovarian Cancer","volume":"10","author":"Czerwonka","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1242\/jcs.00932","article-title":"Overexpression of latent transforming growth factor-beta binding protein 1 (LTBP-1) in dioxin receptor-null mouse embryo fibroblasts","volume":"117","author":"Dallas","year":"2004","journal-title":"J. Cell Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1038\/s41467-018-03556-7","article-title":"nc886 is induced by TGF-\u03b2 and suppresses the microRNA pathway in ovarian cancer","volume":"9","author":"Ahn","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4545","DOI":"10.1038\/s41467-020-17811-3","article-title":"Selective inhibition of TGF-\u03b21 produced by GARP-expressing Tregs overcomes resistance to PD-1\/PD-L1 blockade in cancer","volume":"11","author":"Bertrand","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41571-020-0403-1","article-title":"TGF\u03b2 biology in cancer progression and immunotherapy","volume":"18","author":"Derynck","year":"2021","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/ni1549","article-title":"Smad3 and NFAT cooperate to induce Foxp3 expression through its enhancer","volume":"9","author":"Tone","year":"2008","journal-title":"Nat. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.immuni.2006.07.012","article-title":"Cellular mechanisms of fatal early-onset autoimmunity in mice with the T cell-specific targeting of transforming growth factor-beta receptor","volume":"25","author":"Marie","year":"2006","journal-title":"Immunity"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3262","DOI":"10.1016\/j.celrep.2018.05.050","article-title":"Targeting EZH2 Reprograms Intratumoral Regulatory T Cells to Enhance Cancer Immunity","volume":"23","author":"Wang","year":"2018","journal-title":"Cell Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"44534","DOI":"10.18632\/oncotarget.10003","article-title":"and Pan, S. TGF-\u03b21 contributes to CD8+ Treg induction through p38 MAPK signaling in ovarian cancer microenvironment","volume":"7","author":"Wu","year":"2016","journal-title":"Oncotarget"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/2\/205\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:11:23Z","timestamp":1760119883000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/2\/205"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,20]]},"references-count":43,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["medicina59020205"],"URL":"https:\/\/doi.org\/10.3390\/medicina59020205","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,20]]}}}