{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T10:19:02Z","timestamp":1771928342582,"version":"3.50.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To systematically compare the differences in immune characteristics among three populations (normal group, high-risk group, and esophageal cancer [EC] patients group) and construct a predictive model based on immune metrics, thereby exploring its value in EC risk assessment and early diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 440 participants were enrolled, including 173 normal individuals, 162 high-risk individuals, and 105 EC patients. Peripheral blood samples were collected, and 75 immune metrics were detected using flow cytometry. First, 21 highly correlated indicators were eliminated through the Pearson correlation matrix (|r|\u22650.7), leaving 54 indicators for further analysis. Multivariate analysis of variance (MANOVA) was used to assess the effect of EC grouping on immune metrics, adjusting for gender and age. Significant indicators were analyzed using analysis of covariance (ANCOVA) and the false discovery rate (FDR). Stratified sensitivity analysis was conducted to verify the robustness of the results. Finally, a predictive model was built using 12 key immune metrics, and 10 covariates. The model performance was evaluated by 10-fold cross-validation, neural network algorithm, accuracy, Kappa value, and area under the receiver operating characteristic curve (AUC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MANOVA showed that EC grouping had a significant overall impact on the 54-immune metrics (Pillai = 0.585,\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 2.2\u00d710\n                      <jats:sup>^\u221216<\/jats:sup>\n                      ). After ANCOVA and FDR correction, 12 immune metrics with significant inter-group differences were identified (\n                      <jats:italic>P\u2032<\/jats:italic>\n                      &amp;lt; 0.05), including Tcm CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells, Naive CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, Tem CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, and FB CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells. Stratified sensitivity analysis confirmed stable differences in key indicators (FB CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells and Act NK cells) remained stable among subgroups. The neural network predictive model exhibited excellent discriminative efficacy: the overall cross-validation accuracy was 81.2%, the Kappa value was 0.709, and the AUC values for pairwise comparisons among the three populations were all higher than 0.90 (0.905 to 0.927).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study demonstrates distinct and stable immune profiles across EC risk groups. The immune-based machine learning model effectively differentiates normal, high-risk, and cancer populations, offering a promising non-invasive tool for early risk assessment and screening of esophageal cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1723700","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T06:43:35Z","timestamp":1769755415000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Differences in immune indicators among normal, high-risk, and esophageal cancer populations and development of a predictive model"],"prefix":"10.3389","volume":"17","author":[{"given":"Jian","family":"Li","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Xinxiang Medical University","place":["Xinxiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaoju","family":"Qian","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Xinxiang Medical University","place":["Xinxiang, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Anyang Tumor Hospital & The Affiliated Anyang Tumor Hospital of Henan University of Science and Technology","place":["Anyang, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenchen","family":"Lv","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Xinxiang Medical University","place":["Xinxiang, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiamin","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Xinxiang Medical University","place":["Xinxiang, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaiwen","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Xinxiang Medical University","place":["Xinxiang, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiali","family":"He","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Xinxiang Medical University","place":["Xinxiang, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suli","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Xinxiang Medical University","place":["Xinxiang, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yadi","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Xinxiang Medical University","place":["Xinxiang, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zishan","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Xinxiang Medical University","place":["Xinxiang, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhili","family":"Chu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Xinxiang Medical University","place":["Xinxiang, Henan, China"]},{"name":"Henan International Joint Laboratory of Immunity and Targeted Therapy for Liver-Intestinal Tumors, Xinxiang Medical University","place":["Xinxiang, Henan, China"]},{"name":"Henan Research Center for Engineering Technology in Digestive Tract Tumor Immune Digital Decoding and Cell Therapy, Xinxiang Medical University","place":["Xinxiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Anyang Tumor Hospital & The Affiliated Anyang Tumor Hospital of Henan University of Science and Technology","place":["Anyang, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Ren","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Xinxiang Medical University","place":["Xinxiang, Henan, China"]},{"name":"Henan International Joint Laboratory of Immunity and Targeted Therapy for Liver-Intestinal Tumors, Xinxiang Medical University","place":["Xinxiang, Henan, China"]},{"name":"Henan Research Center for Engineering Technology in Digestive Tract Tumor Immune Digital Decoding and Cell Therapy, Xinxiang Medical University","place":["Xinxiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA: Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(18)30127-X","article-title":"Changing cancer survival in China during 2003\u201315: a pooled analysis of 17 population-based cancer registries","volume":"6","author":"Zeng","year":"2018","journal-title":"Lancet Global Health"},{"key":"B3","doi-asserted-by":"publisher","first-page":"17048","DOI":"10.1038\/nrdp.2017.48","article-title":"Oesophageal cancer","volume":"3","author":"Smyth","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"B4","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of cancer: new dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0014-x","article-title":"Understanding the tumor immune microenvironment (TIME) for effective therapy","volume":"24","author":"Binnewies","year":"2018","journal-title":"Nat Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2019.7337","article-title":"Emerging multimodality approaches to treat localized esophageal cancer","volume":"17","author":"Kelly","year":"2019","journal-title":"J Natl Compr Cancer Network: JNCCN"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.08.023","article-title":"Epidemiology of esophageal squamous cell carcinoma","volume":"154","author":"Abnet","year":"2018","journal-title":"Gastroenterology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1053\/j.gastro.2017.07.007","article-title":"The evolving genomic landscape of barrett\u2019s esophagus and esophageal adenocarcinoma","volume":"153","author":"Contino","year":"2017","journal-title":"Gastroenterology"},{"key":"B9","article-title":"Innate and Adaptive Immune Cells in Tumor Microenvironment[J]","volume":"1","author":"Shrihari","year":"2021","journal-title":"Gulf J Oncol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-042020-042741","article-title":"Immune checkpoint inhibitors for the treatment of cancer: clinical impact and mechanisms of response and resistance","volume":"16","author":"Bagchi","year":"2021","journal-title":"Annu Rev Pathol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1610502","DOI":"10.3389\/pore.2022.1610502","article-title":"The role of tumor microenvironment and immune response in colorectal cancer development and prognosis","volume":"28","author":"Wozniakova","year":"2022","journal-title":"Pathol Oncol research: POR"},{"key":"B12","doi-asserted-by":"publisher","first-page":"6268","DOI":"10.1038\/s41467-020-20019-0","article-title":"Immune suppressive landscape in the human esophageal squamous cell carcinoma microenvironment","volume":"11","author":"Zheng","year":"2020","journal-title":"Nat Commun"},{"key":"B13","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.immuni.2019.12.011","article-title":"Top 10 challenges in cancer immunotherapy","volume":"52","author":"Hegde","year":"2020","journal-title":"Immunity"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-019-0235-4","article-title":"CD8+ T cell states in human cancer: insights from single-cell analysis","volume":"20","author":"van der Leun","year":"2020","journal-title":"Nat Rev Cancer"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.07.010","article-title":"CD8(+) T cells: foot soldiers of the immune system","volume":"35","author":"Zhang","year":"2011","journal-title":"Immunity"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.12836","article-title":"Effect of camrelizumab vs placebo added to chemotherapy on survival and progression-free survival in patients with advanced or metastatic esophageal squamous cell carcinoma: the ESCORT-1st randomized clinical trial","volume":"326","author":"Luo","year":"2021","journal-title":"JAMA"},{"key":"B17","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s40425-018-0367-1","article-title":"Pan-cancer adaptive immune resistance as defined by the Tumor Inflammation Signature (TIS): results from The Cancer Genome Atlas (TCGA)","volume":"6","author":"Danaher","year":"2018","journal-title":"J Immunotherapy Cancer"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000002116","article-title":"ImmunoScore signature: A prognostic and predictive tool in gastric cancer","volume":"267","author":"Jiang","year":"2018","journal-title":"Ann Surg"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21338","article-title":"Cancer statistics in China, 2015","volume":"66","author":"Chen","year":"2016","journal-title":"CA: A Cancer J Clin"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.12.024","article-title":"Individual and combined effects of environmental risk factors for esophageal cancer based on results from the golestan cohort study","volume":"156","author":"Sheikh","year":"2019","journal-title":"Gastroenterology"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.canep.2012.03.001","article-title":"The importance of exposure rate on odds ratios by cigarette smoking and alcohol consumption for esophageal adenocarcinoma and squamous cell carcinoma in the Barrett\u2019s Esophagus and Esophageal Adenocarcinoma Consortium","volume":"36","author":"Lubin","year":"2012","journal-title":"Cancer Epidemiol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.21147\/j.issn.1000-9604.2022.04.02","article-title":"National guidelines for diagnosis and treatment of melanoma 2022 in China (English version)","volume":"34","year":"2022","journal-title":"Chin J Cancer Res"},{"key":"B23","article-title":"Pr\u00e9valence du tabagisme au maghreb: Revue syst\u00e9matique de la litt\u00e9rature et m\u00e9ta analyse Prevalence of smoking in the maghreb: a systematic review and meta-analysis","volume":"96","author":"Serhier","year":"2018","journal-title":"LA TUNISIE MEDICALE"},{"key":"B24","doi-asserted-by":"publisher","first-page":"152427","DOI":"10.1016\/j.comppsych.2023.152427","article-title":"Psychometric properties of the Alcohol Use Disorders Identification Test (AUDIT) across cross-cultural subgroups, genders, and sexual orientations: Findings from the International Sex Survey (ISS)","volume":"127","author":"Horv\u00e1th","year":"2023","journal-title":"Compr Psychiatry"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/nxz268","article-title":"The world cancer research fund\/american institute for cancer research third expert report on diet, nutrition, physical activity, and cancer: impact and future directions","volume":"150","author":"Clinton","year":"2020","journal-title":"J Nutr"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.21147\/j.issn.1000-9604.2022.04.01","article-title":"National guidelines for diagnosis and treatment of esophageal carcinoma 2022 in China (English version)","volume":"34","year":"2022","journal-title":"Chin J Cancer Res"},{"key":"B27","doi-asserted-by":"publisher","first-page":"992","DOI":"10.1016\/j.annonc.2022.07.003","article-title":"Oesophageal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","volume":"33","author":"Obermannov\u00e1","year":"2022","journal-title":"Ann Oncol"},{"key":"B28","volume-title":"Centre international de recherche sur le cancer. A review of human carcinogens","year":"2012"},{"key":"B29","volume-title":"Drinking coffee, mate, and very hot beverages","year":"2018"},{"key":"B30","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1002\/ijc.24445","article-title":"High-temperature beverages and foods and esophageal cancer risk--a systematic review","volume":"125","author":"Islami","year":"2009","journal-title":"Int J Cancer"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.70007","article-title":"Association of oral health and periodontal disease with oesophageal cancer: A nationwide population-based study","volume":"52","author":"Son","year":"2025","journal-title":"J Clin Periodontology"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/his.13975","article-title":"The 2019 WHO classification of tumours of the digestive system","volume":"76","author":"Nagtegaal","year":"2020","journal-title":"Histopathology"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21388","article-title":"The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more \u201cpersonalized\u201d approach to cancer staging","volume":"67","author":"Amin","year":"2017","journal-title":"CA: Cancer J Clin"},{"key":"B34","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.ccell.2022.12.004","article-title":"Integrated multi-omics profiling yields a clinically relevant molecular classification for esophageal squamous cell carcinoma","volume":"41","author":"Liu","year":"2023","journal-title":"Cancer Cell"},{"key":"B35","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1186\/s13059-023-03035-3","article-title":"Comprehensive analyses of partially methylated domains and differentially methylated regions in esophageal cancer reveal both cell-type- and cancer-specific epigenetic regulation","volume":"24","author":"Zheng","year":"2023","journal-title":"Genome Biol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"3700","DOI":"10.1038\/s41467-024-47886-1","article-title":"Multimodal analysis of cfDNA methylomes for early detecting esophageal squamous cell carcinoma and precancerous lesions","volume":"15","author":"Liu","year":"2024","journal-title":"Nat Commun"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1479-5876-10-1","article-title":"The immune score as a new possible approach for the classification of cancer","volume":"10","author":"Galon","year":"2012","journal-title":"J Trans Med"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.immuni.2013.07.012","article-title":"Oncology meets immunology: the cancer-immunity cycle","volume":"39","author":"Chen","year":"2013","journal-title":"Immunity"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.22.012703.104803","article-title":"The three es of cancer immunoediting","volume":"22","author":"Dunn","year":"2004","journal-title":"Annu Rev Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/nri954","article-title":"The lineage decisions of helper T cells","volume":"2","author":"Murphy","year":"2002","journal-title":"Nat Rev Immunol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"e33144","DOI":"10.1016\/j.heliyon.2024.e33144","article-title":"The role of CD8+ T-cells in colorectal cancer immunotherapy","volume":"10","author":"He","year":"2024","journal-title":"Heliyon"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2035","article-title":"T cell exhaustion","volume":"12","author":"Wherry","year":"2011","journal-title":"Nat Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3239","article-title":"The blockade of immune checkpoints in cancer immunotherapy","volume":"12","author":"Pardoll","year":"2012","journal-title":"Nat Rev Cancer"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.05.009","article-title":"Regulatory T cells and immune tolerance","volume":"133","author":"Sakaguchi","year":"2008","journal-title":"Cell"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.25.022106.141623","article-title":"Regulatory T cells: mechanisms of differentiation and function","volume":"30","author":"Josefowicz","year":"2012","journal-title":"Annu Rev Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1723700\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T09:27:39Z","timestamp":1771925259000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1723700\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,30]]},"references-count":45,"alternative-id":["10.3389\/fimmu.2026.1723700"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1723700","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,30]]},"article-number":"1723700"}}