{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T13:04:33Z","timestamp":1783947873087,"version":"3.55.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"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. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To compare CD4+ T cell, CD8+ T cell infiltration and PD-L1 expression between paired biopsy and resection specimens in gastric and colorectal adenocarcinoma, and evaluate their clinical significance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Paired biopsy and resection specimens from 38 gastric and 40 colorectal adenocarcinoma patients were assessed by immunohistochemistry for CD4+ T cell, CD8+ T cell density and PD-L1 expression. Correlations with clinicopathological parameters and tumor markers were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In gastric adenocarcinoma, resection specimens showed significantly higher CD4+ T cell, CD8+ T cell density and PD-L1 expression than biopsies (all P&amp;lt;0.05), with CD4+ T cells positively correlated with CA19-9 (R\u00a0=\u00a00.523, P\u00a0=\u00a00.026). In colorectal adenocarcinoma, CD8+ T cell density was higher in resection specimens (P\u00a0=\u00a00.0353); CD4+ T cells negatively correlated with Ki-67 (R=-0.370, P\u00a0=\u00a00.019), and CD4+\/CD8+ ratio negatively correlated with mismatch repair protein expression (R=-0.342, P\u00a0=\u00a00.029). In both cancers, CD4+\/CD8+ ratios at tumor center and invasive margin were positively correlated (gastric: R\u00a0=\u00a00.5683, P\u00a0=\u00a00.0002; colorectal: R\u00a0=\u00a00.7324, P&amp;lt;0.0001). Preoperative neutrophil-to-lymphocyte ratio positively correlated with tumor diameter in both cancers (gastric: R\u00a0=\u00a00.449, P\u00a0=\u00a00.011; colorectal: R\u00a0=\u00a00.631, P\u00a0=\u00a00.001). CD4+ T cell density differed significantly between cancer types (P &amp;lt;0.0001). ROC analysis demonstrated limited predictive value of biopsy specimens for surgical findings, particularly in colorectal cancer (AUC 0.5-0.7).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Biopsy specimens inadequately represent the immune microenvironment of resection specimens, especially in gastric adenocarcinoma. Tumor-type-specific immune assessment of biopsies is essential for guiding precise immunotherapy decisions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1830997","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T04:33:46Z","timestamp":1782102826000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Differential infiltration of CD4+ and CD8+ T cells and expression of PD-L1 in paired biopsy and resection specimens of gastric and colorectal adenocarcinomas"],"prefix":"10.3389","volume":"16","author":[{"given":"Zi-xuan","family":"Wang","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences, Dali University","place":["Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-mei","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Dali University","place":["Yunnan, China"]},{"name":"Department of Pathology, First Affiliated Hospital of Dali University","place":["Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao-zhen","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Dali University","place":["Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Dali University","place":["Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-jie","family":"Tong","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Dali University","place":["Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Dali University","place":["Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duo","family":"Deng","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Dali University","place":["Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Pan","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Dali University","place":["Yunnan, China"]},{"name":"Department of Pathology, First Affiliated Hospital of Dali University","place":["Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.02.068","article-title":"Global burden of 5 major types of gastrointestinal cancer","volume":"159","author":"Arnold","year":"2020","journal-title":"Gastroenterology"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2025.104941","article-title":"Immunotherapy in gastric adenocarcinoma - a rapidly evolving treatment landscape","volume":"216","author":"Wang","year":"2025","journal-title":"Crit Rev Oncology\/Hematology"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA: A Cancer J For Clin"},{"key":"B4","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA: A Cancer J For Clin"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.2234","article-title":"Prognosis of three histological subtypes of colorectal adenocarcinoma: A retrospective analysis of 8005 Chinese patients","volume":"8","author":"Li","year":"2019","journal-title":"Cancer Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1177\/1010428317714626","article-title":"Progress in the treatment of advanced gastric cancer","volume":"39","author":"Song","year":"2017","journal-title":"Tumour Biol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00534-x","article-title":"The inflammatory pathogenesis of colorectal cancer","volume":"21","author":"Schmitt","year":"2021","journal-title":"Nat Rev Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2021.188615","article-title":"Advances in clinical immunotherapy for gastric cancer","volume":"1876","author":"Li","year":"2021","journal-title":"Biochim Biophys Acta Rev Cancer"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1291117","article-title":"Research progress on the immune microenvironment and immunotherapy in gastric cancer","volume":"14","author":"Mou","year":"2023","journal-title":"Front Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13246206","article-title":"The colorectal cancer tumor microenvironment and its impact on liver and lung metastasis","volume":"13","author":"Chandra","year":"2021","journal-title":"Cancers"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13520","article-title":"Human FOXP3 and tumour microenvironment","volume":"168","author":"Wang","year":"2023","journal-title":"Immunology"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.954992","article-title":"Managing the TME to improve the efficacy of cancer therapy","volume":"13","author":"Bilotta","year":"2022","journal-title":"Front Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2024.104471","article-title":"Advancements in tumor-infiltrating lymphocytes: Historical insights, contemporary milestones, and future directions in oncology therapy","volume":"202","author":"Aizaz","year":"2024","journal-title":"Crit Rev Oncology\/Hematology"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00071","article-title":"Scoring system for tumor-infiltrating lymphocytes and its prognostic value for gastric cancer","volume":"10","author":"Zhang","year":"2019","journal-title":"Front Immunol"},{"key":"B15","doi-asserted-by":"crossref","DOI":"10.1038\/ni.2703","article-title":"Innate and adaptive immune cells in the tumor microenvironment","volume":"14","author":"Gajewski","year":"2013","journal-title":"Nat Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.03.014","article-title":"Regulation and function of the PD-L1 checkpoint","volume":"48","author":"Sun","year":"2018","journal-title":"Immunity"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellin.2024.100146","article-title":"PD-1-mediated inhibition of T cell activation: Mechanisms and strategies for cancer combination immunotherapy","volume":"3","author":"Liu","year":"2024","journal-title":"Cell Insight"},{"key":"B18","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1186\/s12943-024-02023-w","article-title":"Regulatory mechanisms of PD-1\/PD-L1 in cancers","volume":"23","author":"Lin","year":"2024","journal-title":"Mol Cancer"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-090222-110914","article-title":"T cell exhaustion","volume":"12","author":"Wherry","year":"2011","journal-title":"Nat Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-022-00854-y","article-title":"Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons","volume":"20","author":"Naimi","year":"2022","journal-title":"Cell Communication Signaling: CCS"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2025.1530054","article-title":"Nomograms for stratified prognosis prediction of gastric cancer by integrating programmed death ligand 1 and tumor-infiltrating immune cells including CD4+\/CD8+ TILs and CD163+ TAMs","volume":"15","author":"Qi","year":"2025","journal-title":"Front Oncol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.12659\/msm.935348","article-title":"A review of emerging biomarkers for immune checkpoint inhibitors in tumors of the gastrointestinal tract","volume":"28","author":"Liao","year":"2021","journal-title":"Med Sci Monit"},{"key":"B23","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":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-025-04223-9","article-title":"Biology and evolving management of resectable dMMR\/MSI-H cancers: Current status and future perspectives","volume":"74","author":"Tanegashima","year":"2025","journal-title":"Cancer Immunology Immunotherapy: CII"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2017699","article-title":"Pembrolizumab in microsatellite-instability-high advanced colorectal cancer","volume":"383","author":"Andr\u00e9","year":"2020","journal-title":"N Engl J Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan6733","article-title":"Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade","volume":"357","author":"Le","year":"2017","journal-title":"Sci (New York NY)"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.16930","article-title":"An overview of predictive biomarkers and detection approaches for immunotherapy response in GI Malignancies","volume":"40","author":"Chai","year":"2025","journal-title":"J Gastroenterol Hepatol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-019-0515-5","article-title":"Can PD-L1 expression evaluated by biopsy sample accurately reflect its expression in the whole tumour in gastric cancer","volume":"121","author":"Yamashita","year":"2019","journal-title":"Br J Cancer"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-020-02784-5","article-title":"Correlation of tumor microenvironment from biopsy and resection specimens in untreated colorectal cancer patients: A surprising lack of agreement","volume":"70","author":"Kemp Bohan","year":"2021","journal-title":"Cancer Immunology Immunotherapy: CII"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/39.4.561","article-title":"Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine","volume":"39","author":"Zweig","year":"1993","journal-title":"Clin Chem"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2009.237","article-title":"Microsatellite instability in colorectal cancer-the stable evidence","volume":"7","author":"Vilar","year":"2010","journal-title":"Nat Rev Clin Oncol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/s13000-022-01225-4","article-title":"Visual and digital assessment of ki-67 in breast cancer tissue - a comparison of methods","volume":"17","author":"Skjervold","year":"2022","journal-title":"Diagn Pathol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2017.156","article-title":"Implications of the tumor immune microenvironment for staging and therapeutics","volume":"31","author":"Taube","year":"2018","journal-title":"Modern Pathol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14010109","article-title":"Comparative analysis of predictive biomarkers for PD-1\/PD-L1 inhibitors in cancers: Developments and challenges","volume":"14","author":"Yang","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2020.08.025","article-title":"Recurrence rate after loop electrosurgical excision procedure (LEEP) and laser conization: A 5-year follow-up study","volume":"159","author":"Bogani","year":"2020","journal-title":"Gynecologic Oncol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-021-02744-0","article-title":"Tumor microenvironment and its clinicopathological and prognostic associations in surgically resected cutaneous angiosarcoma","volume":"24","author":"Bi","year":"2022","journal-title":"Clin Transl Oncol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1200\/po.24.00230","article-title":"PD-L1 immunohistochemistry in gastric cancer: Comparison of combined positive score and tumor area positivity across 28-8, 22C3, and SP263 assays","volume":"8","author":"Klempner","year":"2024","journal-title":"JCO Precis Oncol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-12-81","article-title":"CD8\/CD45RO T-cell infiltration in endoscopic biopsies of colorectal cancer predicts nodal metastasis and survival","volume":"12","author":"Koelzer","year":"2014","journal-title":"J Transl Med"},{"key":"B39","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":"B40","doi-asserted-by":"publisher","DOI":"10.1007\/s00464-019-07301-z","article-title":"Effect of histologic differences between biopsy and final resection on treatment outcomes in early gastric cancer","volume":"34","author":"Kim","year":"2020","journal-title":"Surg Endoscopy"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2020.153338","article-title":"PD-L1 expression in paired biopsies and surgical specimens in gastric adenocarcinoma: A digital image analysis study","volume":"218","author":"Heo","year":"2021","journal-title":"Pathol Res Pract"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2017.35.15_suppl.e15578","article-title":"Prognostic role of tumor-infiltrating lymphocytes in gastric cancer: A systematic review and meta-analysis","volume":"97","author":"Cao","year":"2018","journal-title":"Medicine"},{"key":"B43","doi-asserted-by":"publisher","first-page":"3928","DOI":"10.1038\/s41467-019-11788-4","article-title":"Macrophage spatial heterogeneity in gastric cancer defined by multiplex immunohistochemistry","volume":"10","author":"Huang","year":"2019","journal-title":"Nat Commun"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1347530","article-title":"Epigenetic modulation of cytokine expression in gastric cancer: Influence on angiogenesis, metastasis and chemoresistance","volume":"15","author":"Reyes","year":"2024","journal-title":"Front Immunol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"138","DOI":"10.3390\/cells12010138","article-title":"The cytokine network in colorectal cancer: Implications for new treatment strategies","volume":"12","author":"Braum\u00fcller","year":"2022","journal-title":"Cells"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-017-1774-3","article-title":"Ki67 targeted strategies for cancer therapy","volume":"20","author":"Yang","year":"2018","journal-title":"Clin Trans Oncol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2014.2914","article-title":"Ki67 is a promising molecular target in the diagnosis of cancer (review)","volume":"11","author":"Li","year":"2015","journal-title":"Mol Med Rep"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3390\/genes14061169","article-title":"Microsatellite instability and immune response: from microenvironment features to therapeutic actionability-lessons from colorectal cancer","volume":"14","author":"Greco","year":"2023","journal-title":"Genes"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.25122\/jml-2022-0173","article-title":"The importance of CA 72-4 and CA 19-9 dosing in gastric cancer","volume":"16","author":"Ro\u0219u","year":"2023","journal-title":"J Med Life"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dju124","article-title":"Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis","volume":"106","author":"Templeton","year":"2014","journal-title":"J Natl Cancer Institute"}],"updated-by":[{"DOI":"10.3389\/fonc.2026.1920220","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000}}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1830997\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T12:04:20Z","timestamp":1783944260000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1830997\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,22]]},"references-count":50,"alternative-id":["10.3389\/fonc.2026.1830997"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1830997","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,22]]},"article-number":"1830997"}}