{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T04:14:28Z","timestamp":1789791268578,"version":"4.0.1"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"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:p>\n                    The tumour immune microenvironment is increasingly recognised as a critical determinant of cancer progression, prognosis, and therapeutic response, challenging the sufficiency of anatomy-based staging systems such as TNM. The Immunoscore (IS), originally validated in colorectal cancer, provides a standardised, spatially resolved assessment of CD3\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells within the tumour core (TC) and invasive margin (IM). Expanding upon this framework, adapted and modified IS models, as well as computational and imaging-based surrogates, have been investigated across multiple solid malignancies, including non-small-cell lung cancer, hepatocellular carcinoma, head and neck cancers, gastric cancer, melanoma, and bladder cancer. This review synthesises the current evidence, emphasising both the translational potential and methodological heterogeneity of IS-based approaches. High IS or adapted scores generally correlate with improved survival and may refine risk stratification, complementing conventional TNM staging. However, inter-study variability limits comparability and reproducibility. Retrospective designs, single-centre cohorts, limited external validation, and potential overfitting in computational models further constrain the strength of evidence. Biological context dependency, immune-exclusion phenotypes, and the dynamic evolution of the tumour immune landscape complicate interpretation, underscoring that high immune cell density does not universally equate to effective antitumour immunity. Overall, the IS and related immune-contexture classifiers constitute a biologically grounded framework that bridges tumour immunology and clinical oncology. While promising, widespread clinical implementation requires methodological harmonisation, prospective validation, and integration with genomic, systemic, and imaging biomarkers. By highlighting both achievements and current limitations, this review provides a balanced perspective on the potential and challenges of translating immune contexture-based metrics into precision oncology.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1832715","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:55:28Z","timestamp":1778219728000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Immunoscore and beyond: evolution and clinical integration of immune contexture-based biomarkers across solid tumours"],"prefix":"10.3389","volume":"17","author":[{"given":"Esteban","family":"Orenes-Pi\u00f1ero","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Murcia","place":["Murcia, Spain"]},{"name":"Proteomic Unit, Instituto Murciano de Investigaciones Biosanitarias (IMIB) Pascual Parrilla","place":["Murcia, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silverio","family":"Ros-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca (HCUVA)","place":["Murcia, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Luis","family":"Alonso-Romero","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca (HCUVA)","place":["Murcia, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Antonio","family":"Ortega-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Paediatric Environmental Health Specialty Unit, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca (HCUVA)","place":["Murcia, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1186\/s12967-017-1310-9","article-title":"World-wide immunoscore task force: meeting report from the \u201cMelanoma Bridge\u201d, Napoli, November 30th-December 3rd, 2016","volume":"15","author":"Galon","year":"2017","journal-title":"J Transl Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1002\/path.4287","article-title":"Towards the introduction of the \u2018immunoscore\u2019 in the classification of Malignant tumors","volume":"232","author":"Galon","year":"2014","journal-title":"J Pathol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1186\/s40425-019-0656-3","article-title":"Immune cell concentrations among the primary tumor microenvironment in colon cancer patients predicted by clinicopathologic characteristics and blood indexes","volume":"7","author":"Guo","year":"2019","journal-title":"J Immunother Cancer"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1080\/10408363.2020.1729692","article-title":"Immunoscore: a novel prognostic tool. Association with clinical outcome, response to treatment and survival in several Malignancies","volume":"57","author":"Ros-Mart\u00ednez","year":"2020","journal-title":"Crit Rev Clin Lab Sci"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1914-8","article-title":"Tertiary lymphoid structures improve immunotherapy and survival in melanoma","volume":"577","author":"Cabrita","year":"2020","journal-title":"Nature"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.865596","article-title":"CD20+CD22+ADAM28+ B cells in tertiary lymphoid structures promote immunotherapy response","volume":"13","author":"Wu","year":"2022","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1016\/j.jtho.2016.01.015","article-title":"The role of tumour-infiltrating lymphocytes in development, progression, and prognosis of non-small cell lung cancer","volume":"11","author":"Bremnes","year":"2016","journal-title":"J Thorac Oncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.18651","article-title":"Programmed cell death-ligand 1 expression and immunoscore in stage II and III non-small cell lung cancer patients receiving adjuvant chemotherapy","volume":"8","author":"Ishii","year":"2017","journal-title":"Oncotarget"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.564915","article-title":"Combined immunoscore for prognostic stratification of early stage non-small-cell lung cancer","volume":"10","author":"Boscolo","year":"2020","journal-title":"Front Oncol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1177\/1758835920984975","article-title":"Clinical impact of the tumour immune microenvironment in completely resected stage IIIA(N2) non-small cell lung cancer based on an immunoscore approach","volume":"13","author":"Feng","year":"2021","journal-title":"Ther Adv Med Oncol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.835630","article-title":"Development and validation of an immune-based prognostic risk score for patients with resected non-small cell lung cancer","volume":"13","author":"He","year":"2022","journal-title":"Front Immunol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"24","DOI":"10.21037\/tlcr-21-751","article-title":"A prediction model integrated genomic alterations and immune signatures of tumour immune microenvironment for early recurrence of stage I NSCLC after curative resection","volume":"11","author":"Hu","year":"2022","journal-title":"Transl Lung Cancer Res"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-022-01225-3","article-title":"Development of a novel combined nomogram model integrating deep learning-pathomics, radiomics and immunoscore to predict postoperative outcome of colorectal cancer lung metastasis patients","volume":"15","author":"Wang","year":"2022","journal-title":"J Hematol Oncol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1016\/j.jhep.2019.12.014","article-title":"Heterogeneous immunogenomic features and distinct escape mechanisms in multifocal hepatocellular carcinoma","volume":"72","author":"Dong","year":"2020","journal-title":"J Hepatol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s43657-023-00136-8","article-title":"Noninvasive approach to evaluate tumour immune microenvironment and predict outcomes in hepatocellular carcinoma","volume":"3","author":"Wu","year":"2023","journal-title":"Phenomics"},{"key":"B16","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1111\/cas.16449","article-title":"Comparison of 11C-acetate and 18F-FDG PET\/CT for immune infiltration and prognosis in hepatocellular carcinoma","volume":"116","author":"Xu","year":"2025","journal-title":"Cancer Sci"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17060948","article-title":"Immunoscore predicted by dynamic contrast-enhanced computed tomography can be a non-invasive biomarker for immunotherapy susceptibility of hepatocellular carcinoma","volume":"17","author":"Ueshima","year":"2025","journal-title":"Cancers (Basel)"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.17901","article-title":"Characterization of tumour-associated T-lymphocyte subsets and immune checkpoint molecules in head and neck squamous cell carcinoma","volume":"8","author":"Lechner","year":"2017","journal-title":"Oncotarget"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2018.07.012","article-title":"Prognostic and predictive values of immune infiltrate in patients with head and neck squamous cell carcinoma","volume":"82","author":"Zhang","year":"2018","journal-title":"Hum Pathol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32571","article-title":"Development and validation of a seven-immune-feature-based prognostic score for oral squamous cell carcinoma after curative resection","volume":"146","author":"Zhou","year":"2020","journal-title":"Int J Cancer"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-022-04469-1","article-title":"The role of systemic inflammatory response index (SIRI) and tumour-infiltrating lymphocytes (TILs) in the prognosis of patients with laryngeal squamous cell carcinoma","volume":"149","author":"Wang","year":"2023","journal-title":"J Cancer Res Clin Oncol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1097\/JS9.0000000000003559","article-title":"Combined immunescore and pan-immune inflammation value associate with pathological response and survival outcomes in esophageal squamous cell carcinoma receiving neoadjuvant immunotherapy","volume":"112","author":"Huang","year":"2025","journal-title":"Int J Surg"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1163565","article-title":"Tumour-infiltrating lymphocytes and tumour-associated macrophages as potential predictors of lymph node metastases in major salivary gland cancers","volume":"10","author":"De Virgilio","year":"2023","journal-title":"Front Med (Lausanne)"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-16-0381","article-title":"A four-factor immunoscore system that predicts clinical outcome for stage II\/III gastric cancer","volume":"5","author":"Wen","year":"2017","journal-title":"Cancer Immunol Res"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.19439","article-title":"Combined prognostic effect of PD-L1 expression and immunoscore in microsatellite-unstable advanced gastric cancers","volume":"8","author":"Kim","year":"2017","journal-title":"Oncotarget"},{"key":"B26","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":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.621623","article-title":"An immune cell signature is associated with disease-free survival and adjuvant chemosensitivity of patients with resectable gastric cancer","volume":"11","author":"Yan","year":"2021","journal-title":"Front Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1177\/17588359241287747","article-title":"A biopsy-based immunoscore in patients with treatment-na\u00efve resectable gastric cancer","volume":"16","author":"Soeratram","year":"2024","journal-title":"Ther Adv Med Oncol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s40425-015-0091-z","article-title":"Multispectral imaging of formalin-fixed tissue predicts ability to generate tumour-infiltrating lymphocytes from melanoma","volume":"3","author":"Feng","year":"2015","journal-title":"J Immunother Cancer"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102556","article-title":"Robust immunoscore model to predict the response to anti-PD1 therapy in melanoma","volume":"11","author":"Nie","year":"2019","journal-title":"Aging (Albany NY)"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.02105","article-title":"Tumour-infiltrating lymphocytes and their prognostic value in cutaneous melanoma","volume":"11","author":"Maibach","year":"2020","journal-title":"Front Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.18632\/aging.202279","article-title":"Exploration of the immune cell infiltration-related gene signature in the prognosis of melanoma","volume":"13","author":"Zeng","year":"2021","journal-title":"Aging (Albany NY)"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2015.1057388","article-title":"Density of tumour-infiltrating lymphocytes correlates with extent of brain edema and overall survival time in patients with brain metastases","volume":"5","author":"Berghoff","year":"2015","journal-title":"Oncoimmunology"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21218407","article-title":"High stroma T-cell infiltration is associated with better survival in stage pT1 bladder cancer","volume":"21","author":"H\u00fclsen","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B35","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1186\/s12894-022-01085-6","article-title":"Prognostic significance of immunoscore related markers in bladder cancer","volume":"22","author":"Ariafar","year":"2022","journal-title":"BMC Urol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics12061360","article-title":"Modified immunoscore improves prediction of survival outcomes in patients undergoing radical cystectomy for bladder cancer-a retrospective digital pathology study","volume":"12","author":"Bieri","year":"2022","journal-title":"Diagnostics (Basel)"},{"key":"B37","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s40164-024-00543-1","article-title":"Tumor battlefield within inflamed, excluded or desert immune phenotypes: the mechanisms and strategies","volume":"13","author":"Zheng","year":"2024","journal-title":"Exp Hematol Oncol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.ccell.2023.02.016","article-title":"The evolving tumor microenvironment: from cancer initiation to metastatic outgrowth","volume":"41","author":"de Visser","year":"2023","journal-title":"Cancer Cell"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2017.7013","article-title":"Stromal and intraepithelial tumor-infiltrating lymphocytes in colorectal carcinoma","volume":"14","author":"Jakubowska","year":"2017","journal-title":"Oncol Lett"},{"key":"B40","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1038\/s41392-024-01979-x","article-title":"Cold and hot tumors: from molecular mechanisms to targeted therapy","volume":"9","author":"Wu","year":"2024","journal-title":"Signal Transduct Target Ther"},{"key":"B41","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1038\/s41392-025-02280-1","article-title":"Immune evasion in cancer: mechanisms and cutting-edge therapeutic approaches","volume":"10","author":"Tufail","year":"2025","journal-title":"Signal Transduct Target Ther"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1709852","article-title":"Terminally exhausted CD8+ T cells in solid tumors: biology, biomarker potential and translational tools for precision oncology","volume":"16","author":"Guo","year":"2026","journal-title":"Front Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2020.07.022","article-title":"FoxP3+ T regulatory cells in cancer: prognostic biomarkers and therapeutic targets","volume":"490","author":"Saleh","year":"2020","journal-title":"Cancer Lett"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1517959","article-title":"Immunocytes in the tumor microenvironment: recent updates and interconnections","volume":"16","author":"Yu","year":"2025","journal-title":"Front Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1832715\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:55:29Z","timestamp":1778219729000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1832715\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,8]]},"references-count":44,"alternative-id":["10.3389\/fimmu.2026.1832715"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1832715","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,8]]},"article-number":"1832715"}}