{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:09:03Z","timestamp":1791389343071,"version":"4.3.3"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T00:00:00Z","timestamp":1739491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004761","name":"Natural Science Foundation of Hainan Province","doi-asserted-by":"publisher","award":["823RC594"],"award-info":[{"award-number":["823RC594"]}],"id":[{"id":"10.13039\/501100004761","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>T follicular helper (TFH) cells, a subset of CD4<jats:sup>+<\/jats:sup>Th cells, play a critical role in B cell activation, proliferation, and differentiation primarily within B follicles in secondary lymphoid organs, essential processes for effective antibody responses. TFH cells are also implicated in various conditions, including autoimmune diseases, cancer, infectious diseases, allergies, and vaccine reactions. Despite their broad impact, a review of the literature on TFH cells and tumors has not been conducted. We aimed to fill this gap by providing a detailed analysis of the research landscape concerning TFH cells and tumors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We conducted a bibliometric analysis of literature on TFH cells and tumors from 2012 to 2024 using the Web of Science Core Collection (WoSCC). For an analysis of the global research landscape, we employed VOSviewer (version 1.6.20), CiteSpace 6.2.R6 software, and the \u201cbibliometric\u201d package in R language (version 4.3.2) to evaluate data on countries\/regions, authors and cited authors, institutions, journals, references, and keywords. We also conducted a systematic review to summarize the global research trends, prospects, and hotspots in this field.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our analysis included contributions from 60 countries\/regions, 7,864 authors, 35,853 cited authors, 1,756 institutions, 385 academic journals, 50883 references, 222 keywords, and 1,181published papers. Over the past decade, the volume of research on TFH cells and tumors had consistently increased. China published the most papers, more than double that of the United States. The top 2 authors ranked by publication volume were Gaulard, Philippe (14 articles, 379 citations), and De leval, Laurence (12 articles, 236 citations) Notably, 9 of the top 10 most published institutions were from China. Frontiers in Immunology and Immunity were the leading journals in publications and citations. A cluster analysis revealed a shift in research focus from \u201cexpression\u201d,\u201dB cells\u201d and \u201csurvival\u201d to \u201ctumor microenvironment\u201d, \u201ctumor infiltrating immune cells\u201d and \u201cimmune infiltration\u201d in recent years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This bibliometric analysis suggests that TFH cells hold significant research value and potential clinical applications in tumor immunotherapy. Moreover, the bibliometric analysis offers valuable references and guidance for related research endeavors. It also points out the prevailing issues and challenges in TFH cell research, and underscores the need for further basic and clinical research to advance the related fields.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2025.1443890","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T05:11:03Z","timestamp":1739509863000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Global research prospects and trends in TFH cells and tumors: a bibliometric analysis"],"prefix":"10.3389","volume":"15","author":[{"given":"Hao","family":"Lei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junpeng","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runze","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqi","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guisheng","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuping","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hengyu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-041015-055605","article-title":"Follicular helper T cells","volume":"34","author":"Vinuesa","year":"2016","journal-title":"Annu Rev Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-031210-101400","article-title":"Follicular helper CD4 T cells (TFH)","volume":"29","author":"Crotty","year":"2011","journal-title":"Annu Rev Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1126\/science.1175870","article-title":"Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation","volume":"325","author":"Johnston","year":"2009","journal-title":"Science"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1126\/science.1176676","article-title":"Bcl6 mediates the development of T follicular helper cells","volume":"325","author":"Nurieva","year":"2009","journal-title":"Science"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.07.002","article-title":"The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment","volume":"31","author":"Yu","year":"2009","journal-title":"Immunity"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20141380","article-title":"BCL6 orchestrates Tfh cell differentiation via multiple distinct mechanisms","volume":"212","author":"Hatzi","year":"2015","journal-title":"J Exp Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-024-01254-7","article-title":"Transcriptional regulation of Tfh dynamics and the formation of immunological synapses","volume":"56","author":"Kim","year":"2024","journal-title":"Exp Mol Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2021.04.006","article-title":"Cytokine-skewed Tfh cells: functional consequences for B cell help","volume":"42","author":"Olatunde","year":"2021","journal-title":"Trends Immunol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"101448","DOI":"10.1016\/j.xcrm.2024.101448","article-title":"An immune cell map of human lung adenocarcinoma development reveals an anti-tumoral role of the Tfh-dependent tertiary lymphoid structure","volume":"5","author":"Liu","year":"2024","journal-title":"Cell Rep Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.05.009","article-title":"Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages","volume":"29","author":"Nurieva","year":"2008","journal-title":"Immunity"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091706","article-title":"B cell-intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans","volume":"207","author":"Avery","year":"2010","journal-title":"J Exp Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2022.12.007","article-title":"T follicular helper cells in cancer","volume":"9","author":"Guti\u00e9rrez-Melo","year":"2023","journal-title":"Trends Cancer"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1252389","article-title":"Global research landscape and trends of papillary thyroid cancer therapy: a bibliometric analysis","volume":"14","author":"Song","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0307513100","article-title":"Searching for intellectual turning points: progressive knowledge domain visualization","author":"Chen","year":"2004","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s11192-009-0146-3","article-title":"Software survey: VOSviewer, a computer program for bibliometric mapping","volume":"84","author":"van Eck","year":"2010","journal-title":"Scientometrics"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06348-2","article-title":"Rewiring cancer drivers to activate apoptosis","volume":"620","author":"Gourisankar","year":"2023","journal-title":"Nature"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-002588","article-title":"T follicular helper cells: linking cancer immunotherapy and immune-related adverse events","volume":"9","author":"Baumjohann","year":"2021","journal-title":"J Immunother Cancer"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20240959","article-title":"MCRS1 sensitizes T cell-dependent immunotherapy by augmenting MHC-I expression in solid tumors","volume":"221","author":"Li","year":"2024","journal-title":"J Exp Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2912","article-title":"The E3 ubiquitin ligase Itch is required for the differentiation of follicular helper T cells","volume":"15","author":"Xiao","year":"2014","journal-title":"Nat Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4113","article-title":"PD-1(+) and follicular helper T cells are responsible for persistent HIV-1 transcription in treated aviremic individuals","volume":"22","author":"Banga","year":"2016","journal-title":"Nat Med"},{"key":"B21","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1038\/ni.2182","article-title":"Divergent expression patterns of IL-4 and IL-13 define unique functions in allergic immunity","volume":"13","author":"Liang","year":"2011","journal-title":"Nat Immunol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1038\/s41467-018-03493-5","article-title":"Apolipoprotein AI prevents regulatory to follicular helper T cell switching during atherosclerosis","volume":"9","author":"Gaddis","year":"2018","journal-title":"Nat Commun"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.14142","article-title":"Renal operational tolerance is associated with a defect of blood Tfh cells that exhibit impaired B cell help","volume":"17","author":"Chenouard","year":"2017","journal-title":"Am J Transplant"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12576","article-title":"Follicular T helper cells and humoral reactivity in kidney transplant patients","volume":"180","author":"de Graav","year":"2015","journal-title":"Clin Exp Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3337","article-title":"Robust enumeration of cell subsets from tissue expression profiles","volume":"12","author":"Newman","year":"2015","journal-title":"Nat Methods"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.10.003","article-title":"Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer","volume":"39","author":"Bindea","year":"2013","journal-title":"Immunity"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1172\/JCI67428","article-title":"CD4+ follicular helper T cell infiltration predicts breast cancer survival","volume":"123","author":"Gu-Trantien","year":"2013","journal-title":"J Clin Invest"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/nature24302","article-title":"Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity","volume":"551","author":"Shalapour","year":"2017","journal-title":"Nature"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01253-8","article-title":"Targeting T(FH) cells in human diseases and vaccination: rationale and practice","volume":"23","author":"Yu","year":"2022","journal-title":"Nat Immunol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"R921","DOI":"10.1016\/j.cub.2020.06.081","article-title":"The tumor microenvironment","volume":"30","author":"Anderson","year":"2020","journal-title":"Curr Biol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0306-5","article-title":"A guide to cancer immunotherapy: from T cell basic science to clinical practice","volume":"20","author":"Waldman","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.2147\/ITT.S61647","article-title":"CD28 co-stimulation in T-cell homeostasis: a recent perspective","volume":"4","author":"Beyersdorf","year":"2015","journal-title":"Immunotargets Ther"},{"key":"B33","doi-asserted-by":"publisher","first-page":"5066","DOI":"10.1038\/s41467-020-18828-4","article-title":"Structural characterization of the ICOS\/ICOS-L immune complex reveals high molecular mimicry by therapeutic antibodies","volume":"11","author":"Rujas","year":"2020","journal-title":"Nat Commun"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-010-9223-6","article-title":"Interactions between lymphocytes and myeloid cells regulate pro- versus anti-tumor immunity","volume":"29","author":"DeNardo","year":"2010","journal-title":"Cancer Metastasis Rev"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/nri2729","article-title":"Effector and regulatory B cells: modulators of CD4+ T cell immunity","volume":"10","author":"Lund","year":"2010","journal-title":"Nat Rev Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1126\/science.1201730","article-title":"Different B cell populations mediate early and late memory during an endogenous immune response","volume":"331","author":"Pape","year":"2011","journal-title":"Science"},{"key":"B37","doi-asserted-by":"publisher","first-page":"6101","DOI":"10.1016\/j.cell.2021.11.007","article-title":"Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses","volume":"184","author":"Cui","year":"2021","journal-title":"Cell"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.11.013","article-title":"Tfh cells set the stage for tumor control","volume":"54","author":"King","year":"2021","journal-title":"Immunity"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.600886","article-title":"Resolving the paradox of colon cancer through the integration of genetics, immunology, and the microbiota","volume":"11","author":"Fidelle","year":"2020","journal-title":"Front Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2009.416","article-title":"Immune infiltration in human tumors: a prognostic factor that should not be ignored","volume":"29","author":"Pag\u00e8s","year":"2010","journal-title":"Oncogene"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.4.1829","article-title":"Antigen-driven oligoclonal expansion of tumor-infiltrating B cells in infiltrating ductal carcinoma of the breast","volume":"169","author":"Coronella","year":"2002","journal-title":"J Immunol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.15.0284","article-title":"Long-term survival for patients with non-small-cell lung cancer with intratumoral lymphoid structures","volume":"26","author":"Dieu-Nosjean","year":"2008","journal-title":"J Clin Oncol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-0431","article-title":"Human solid tumors contain high endothelial venules: association with T- and B-lymphocyte infiltration and favorable prognosis in breast cancer","volume":"71","author":"Martinet","year":"2011","journal-title":"Cancer Res"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-22-0201","article-title":"Escherichia coli-Specific CXCL13-Producing TFH Are Associated with Clinical Efficacy of Neoadjuvant PD-1 Blockade against Muscle-Invasive Bladder Cancer","volume":"12","author":"Goubet","year":"2022","journal-title":"Cancer Discovery"},{"key":"B45","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1158\/2326-6066.CIR-23-0786","article-title":"SIRT3 negatively regulates TFH-cell differentiation in cancer","volume":"12","author":"Hou","year":"2024","journal-title":"Cancer Immunol Res"},{"key":"B46","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.immuni.2023.12.009","article-title":"Nutritional regulation of microbiota-derived metabolites: Implications for immunity and inflammation","volume":"57","author":"Arifuzzaman","year":"2024","journal-title":"Immunity"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1156212","article-title":"Targeting immune checkpoints in anti-neutrophil cytoplasmic antibodies associated vasculitis: the potential therapeutic targets in the future","volume":"14","author":"Pan","year":"2023","journal-title":"Front Immunol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1176994","article-title":"Antigen presentation by clonally diverse CXCR5+ B cells to CD4 and CD8 T cells is associated with durable response to immune checkpoint inhibitors","volume":"14","author":"Ding","year":"2023","journal-title":"Front Immunol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1176994","article-title":"Progress of IL-21 and Tfh mediated immunotherapy in non-small cell lung cancer","volume":"27","author":"Liu","year":"2024","journal-title":"Zhongguo Fei Ai Za Zhi"},{"key":"B50","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1186\/s13046-024-03179-5","article-title":"In vivo CAR T cell therapy against angioimmunoblastic T cell lymphoma","volume":"43","author":"Krug","year":"2024","journal-title":"J Exp Clin Cancer Res"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1443890\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T05:11:07Z","timestamp":1739509867000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1443890\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,14]]},"references-count":50,"alternative-id":["10.3389\/fonc.2025.1443890"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2025.1443890","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,14]]},"article-number":"1443890"}}