{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:12:28Z","timestamp":1783901548433,"version":"3.55.0"},"reference-count":149,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Precis. Onc."],"DOI":"10.1038\/s41698-026-01330-3","type":"journal-article","created":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T23:09:12Z","timestamp":1783897752000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumor infiltrating lymphocytes in glioblastoma: immunobiology and translational implications"],"prefix":"10.1038","volume":"10","author":[{"given":"Cameron M.","family":"Hill","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chibueze D.","family":"Nwagwu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel O.","family":"Odukoya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Hsueh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony Z.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin P.","family":"Dunn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"1330_CR1","doi-asserted-by":"publisher","first-page":"1935","DOI":"10.1093\/neuonc\/noac116","volume":"24","author":"M Lim","year":"2022","unstructured":"Lim, M. et al. Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter. Neuro. Oncol. 24, 1935\u20131949 (2022).","journal-title":"Neuro. Oncol."},{"key":"1330_CR2","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1016\/S1470-2045(17)30517-X","volume":"18","author":"M Weller","year":"2017","unstructured":"Weller, M. et al. Rindopepimut with temozolomide for patients with newly diagnosed, EGFRvIII-expressing glioblastoma (ACT IV): a randomised, double-blind, international phase 3 trial. Lancet Oncol. 18, 1373\u20131385 (2017).","journal-title":"Lancet Oncol."},{"key":"1330_CR3","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1056\/NEJMoa043330","volume":"352","author":"R Stupp","year":"2005","unstructured":"Stupp, R. et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 352, 987\u2013996 (2005).","journal-title":"N. Engl. J. Med."},{"key":"1330_CR4","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1227\/NEU.0b013e31824f840d","volume":"71","author":"GP Dunn","year":"2012","unstructured":"Dunn, G. P., Fecci, P. E. & Curry, W. T. Cancer immunoediting in malignant glioma. Neurosurgery 71, 201\u2013222 (2012).","journal-title":"Neurosurgery"},{"key":"1330_CR5","first-page":"iv41","volume":"7","author":"CM Hill","year":"2025","unstructured":"Hill, C. M. et al. Immunologic specificity in glioblastoma: antigen discovery and translational implications. Neurooncol. Adv. 7, iv41\u2013iv70 (2025).","journal-title":"Neurooncol. Adv."},{"key":"1330_CR6","doi-asserted-by":"publisher","first-page":"2729","DOI":"10.1158\/1078-0432.CCR-23-3077","volume":"30","author":"TM Johanns","year":"2024","unstructured":"Johanns, T. M. et al. Integrating multisector molecular characterization into personalized peptide vaccine design for patients with newly diagnosed glioblastoma. Clin. Cancer Res. 30, 2729\u20132742 (2024).","journal-title":"Clin. Cancer Res."},{"key":"1330_CR7","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.semcancer.2021.03.002","volume":"78","author":"R Desai","year":"2022","unstructured":"Desai, R., Coxon, A. T. & Dunn, G. P. Therapeutic applications of the cancer immunoediting hypothesis. Semin. Cancer Biol. 78, 63\u201377 (2022).","journal-title":"Semin. Cancer Biol."},{"key":"1330_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.immuni.2013.07.012","volume":"39","author":"DS Chen","year":"2013","unstructured":"Chen, D. S. & Mellman, I. Oncology meets immunology: the cancer-immunity cycle. Immunity 39, 1\u201310 (2013).","journal-title":"Immunity"},{"key":"1330_CR9","doi-asserted-by":"publisher","first-page":"2188","DOI":"10.1016\/j.immuni.2023.09.011","volume":"56","author":"I Mellman","year":"2023","unstructured":"Mellman, I., Chen, D. S., Powles, T. & Turley, S. J. The cancer-immunity cycle: Indication, genotype, and immunotype. Immunity 56, 2188\u20132205 (2023).","journal-title":"Immunity"},{"key":"1330_CR10","doi-asserted-by":"publisher","first-page":"vii3","DOI":"10.1093\/neuonc\/nov175","volume":"17","author":"GP Dunn","year":"2015","unstructured":"Dunn, G. P. & Okada, H. Principles of immunology and its nuances in the central nervous system. Neuro. Oncol. 17, vii3\u2013vii8 (2015).","journal-title":"Neuro. Oncol."},{"key":"1330_CR11","first-page":"58","volume":"29","author":"PB Medawar","year":"1948","unstructured":"Medawar, P. B. Immunity to homologous grafted skin; the fate of skin homografts transplanted to the brain, to subcutaneous tissue, and to the anterior chamber of the eye. Br. J. Exp. Pathol. 29, 58\u201369 (1948).","journal-title":"Br. J. Exp. Pathol."},{"key":"1330_CR12","doi-asserted-by":"publisher","first-page":"eabo7649","DOI":"10.1126\/science.abo7649","volume":"380","author":"G Castellani","year":"2023","unstructured":"Castellani, G., Croese, T., Peralta Ramos, J. M. & Schwartz, M. Transforming the understanding of brain immunity. Science 380, eabo7649 (2023).","journal-title":"Science"},{"key":"1330_CR13","doi-asserted-by":"publisher","first-page":"4216","DOI":"10.1523\/JNEUROSCI.3441-12.2013","volume":"33","author":"CL Cunningham","year":"2013","unstructured":"Cunningham, C. L., Mart\u00ednez-Cerde\u00f1o, V. & Noctor, S. C. Microglia regulate the number of neural precursor cells in the developing cerebral cortex. J. Neurosci. 33, 4216\u20134233 (2013).","journal-title":"J. Neurosci."},{"key":"1330_CR14","doi-asserted-by":"publisher","first-page":"eabk1131","DOI":"10.1126\/sciadv.abk1131","volume":"7","author":"EN Santos","year":"2021","unstructured":"Santos, E. N. & Fields, R. D. Regulation of myelination by microglia. Sci. Adv. 7, eabk1131 (2021).","journal-title":"Sci. Adv."},{"key":"1330_CR15","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/j.neuron.2012.03.026","volume":"74","author":"DP Schafer","year":"2012","unstructured":"Schafer, D. P. et al. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74, 691\u2013705 (2012).","journal-title":"Neuron"},{"key":"1330_CR16","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1158\/2326-6066.CIR-22-0098","volume":"11","author":"JA Bowman-Kirigin","year":"2023","unstructured":"Bowman-Kirigin, J. A. et al. The conventional dendritic cell 1 subset primes CD8+ T cells and traffics tumor antigen to drive antitumor immunity in the brain. Cancer Immunol. Res. 11, 20\u201337 (2023).","journal-title":"Cancer Immunol. Res."},{"key":"1330_CR17","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1038\/s41593-018-0227-9","volume":"21","author":"A Louveau","year":"2018","unstructured":"Louveau, A. et al. CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nat. Neurosci. 21, 1380\u20131391 (2018).","journal-title":"Nat. Neurosci."},{"key":"1330_CR18","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/nature14432","volume":"523","author":"A Louveau","year":"2015","unstructured":"Louveau, A. et al. Structural and functional features of central nervous system lymphatic vessels. Nature 523, 337\u2013341 (2015).","journal-title":"Nature"},{"key":"1330_CR19","doi-asserted-by":"publisher","first-page":"1000","DOI":"10.1016\/j.cell.2020.12.040","volume":"184","author":"J Rustenhoven","year":"2021","unstructured":"Rustenhoven, J. et al. Functional characterization of the dural sinuses as a neuroimmune interface. Cell 184, 1000\u20131016.e27 (2021).","journal-title":"Cell"},{"key":"1330_CR20","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-022-01051-9","volume":"14","author":"AZ Wang","year":"2022","unstructured":"Wang, A. Z. et al. Single-cell profiling of human dura and meningioma reveals cellular meningeal landscape and insights into meningioma immune response. Genome Med. 14, 49 (2022).","journal-title":"Genome Med."},{"key":"1330_CR21","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1126\/science.adc8810","volume":"379","author":"K M\u00f8llg\u00e5rd","year":"2023","unstructured":"M\u00f8llg\u00e5rd, K. et al. A mesothelium divides the subarachnoid space into functional compartments. Science 379, 84\u201388 (2023).","journal-title":"Science"},{"key":"1330_CR22","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1038\/s41586-024-07202-9","volume":"628","author":"Z Fitzpatrick","year":"2024","unstructured":"Fitzpatrick, Z. et al. Venous-plexus-associated lymphoid hubs support meningeal humoral immunity. Nature 628, 612\u2013619 (2024).","journal-title":"Nature"},{"key":"1330_CR23","doi-asserted-by":"publisher","first-page":"3056","DOI":"10.1016\/j.cell.2021.04.003","volume":"184","author":"N Dani","year":"2021","unstructured":"Dani, N. et al. A cellular and spatial map of the choroid plexus across brain ventricles and ages. Cell 184, 3056\u20133074.e21 (2021).","journal-title":"Cell"},{"key":"1330_CR24","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1126\/science.1252945","volume":"346","author":"K Baruch","year":"2014","unstructured":"Baruch, K. et al. Aging. Aging-induced type I interferon response at the choroid plexus negatively affects brain function. Science 346, 89\u201393 (2014).","journal-title":"Science"},{"key":"1330_CR25","doi-asserted-by":"publisher","first-page":"3427","DOI":"10.1093\/brain\/awt259","volume":"136","author":"G Kunis","year":"2013","unstructured":"Kunis, G. et al. IFN-\u03b3-dependent activation of the brain\u2019s choroid plexus for CNS immune surveillance and repair. Brain 136, 3427\u20133440 (2013).","journal-title":"Brain"},{"key":"1330_CR26","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1038\/s41593-018-0213-2","volume":"21","author":"F Herisson","year":"2018","unstructured":"Herisson, F. et al. Direct vascular channels connect skull bone marrow and the brain surface enabling myeloid cell migration. Nat. Neurosci. 21, 1209\u20131217 (2018).","journal-title":"Nat. Neurosci."},{"key":"1330_CR27","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/s41593-018-0301-3","volume":"22","author":"R Cai","year":"2019","unstructured":"Cai, R. et al. Panoptic imaging of transparent mice reveals whole-body neuronal projections and skull-meninges connections. Nat. Neurosci. 22, 317\u2013327 (2019).","journal-title":"Nat. Neurosci."},{"key":"1330_CR28","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf7844","volume":"373","author":"A Cugurra","year":"2021","unstructured":"Cugurra, A. et al. Skull and vertebral bone marrow are myeloid cell reservoirs for the meninges and CNS parenchyma. Science 373, eabf7844 (2021).","journal-title":"Science"},{"key":"1330_CR29","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf9277","volume":"373","author":"S Brioschi","year":"2021","unstructured":"Brioschi, S. et al. Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders. Science 373, eabf9277 (2021).","journal-title":"Science"},{"key":"1330_CR30","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1146\/annurev-immunol-032414-112240","volume":"33","author":"SW Brubaker","year":"2015","unstructured":"Brubaker, S. W., Bonham, K. S., Zanoni, I. & Kagan, J. C. Innate immune pattern recognition: a cell biological perspective. Annu. Rev. Immunol. 33, 257\u2013290 (2015).","journal-title":"Annu. Rev. Immunol."},{"key":"1330_CR31","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/cdd.2013.72","volume":"21","author":"T Yamazaki","year":"2014","unstructured":"Yamazaki, T. et al. Defective immunogenic cell death of HMGB1-deficient tumors: compensatory therapy with TLR4 agonists. Cell Death Differ. 21, 69\u201378 (2014).","journal-title":"Cell Death Differ."},{"key":"1330_CR32","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-03221-2","volume":"11","author":"J Fucikova","year":"2020","unstructured":"Fucikova, J. et al. Detection of immunogenic cell death and its relevance for cancer therapy. Cell Death Dis. 11, 1013 (2020).","journal-title":"Cell Death Dis."},{"key":"1330_CR33","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1016\/j.immuni.2014.10.019","volume":"41","author":"L Deng","year":"2014","unstructured":"Deng, L. et al. STING-dependent cytosolic DNA sensing promotes radiation-induced type I interferon-dependent antitumor immunity in immunogenic tumors. Immunity 41, 843\u2013852 (2014).","journal-title":"Immunity"},{"key":"1330_CR34","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.molimm.2017.12.001","volume":"110","author":"RE Vatner","year":"2019","unstructured":"Vatner, R. E. & Janssen, E. M. STING, DCs and the link between innate and adaptive tumor immunity. Mol. Immunol. 110, 13\u201323 (2019).","journal-title":"Mol. Immunol."},{"key":"1330_CR35","doi-asserted-by":"publisher","first-page":"1808","DOI":"10.1158\/2159-8290.CD-20-0522","volume":"10","author":"D Sha","year":"2020","unstructured":"Sha, D. et al. Tumor mutational burden as a predictive biomarker in solid tumors. Cancer Discov. 10, 1808\u20131825 (2020).","journal-title":"Cancer Discov."},{"key":"1330_CR36","doi-asserted-by":"publisher","first-page":"770561","DOI":"10.3389\/fonc.2021.770561","volume":"11","author":"BT Himes","year":"2021","unstructured":"Himes, B. T. et al. Immunosuppression in glioblastoma: Current understanding and therapeutic implications. Front. Oncol. 11, 770561 (2021).","journal-title":"Front. Oncol."},{"key":"1330_CR37","doi-asserted-by":"crossref","unstructured":"Soeda, A. et al. The evidence of glioblastoma heterogeneity. Sci. Rep. 5, 7979 (2015).","DOI":"10.1038\/srep07979"},{"key":"1330_CR38","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1038\/ng.3590","volume":"48","author":"J Wang","year":"2016","unstructured":"Wang, J. et al. Clonal evolution of glioblastoma under therapy. Nat. Genet. 48, 768\u2013776 (2016).","journal-title":"Nat. Genet."},{"key":"1330_CR39","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1158\/2159-8290.CD-21-0291","volume":"12","author":"MO Schaettler","year":"2022","unstructured":"Schaettler, M. O. et al. Characterization of the genomic and immunologic diversity of malignant brain tumors through multisector analysis. Cancer Discov. 12, 154\u2013171 (2022).","journal-title":"Cancer Discov."},{"key":"1330_CR40","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1093\/neuonc\/noaa154","volume":"22","author":"GP Dunn","year":"2020","unstructured":"Dunn, G. P. et al. Emerging immunotherapies for malignant glioma: from immunogenomics to cell therapy. Neuro. Oncol. 22, 1425\u20131438 (2020).","journal-title":"Neuro. Oncol."},{"key":"1330_CR41","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1007\/s11864-024-01200-9","volume":"25","author":"AF Wang","year":"2024","unstructured":"Wang, A. F., Hsueh, B., Choi, B. D., Gerstner, E. R. & Dunn, G. P. Immunotherapy for brain tumors: Where we have been, and where do we go from here?. Curr. Treat. Options Oncol. 25, 628\u2013643 (2024).","journal-title":"Curr. Treat. Options Oncol."},{"key":"1330_CR42","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1158\/2326-6066.CIR-16-0156","volume":"4","author":"TM Johanns","year":"2016","unstructured":"Johanns, T. M. et al. Endogenous neoantigen-specific CD8 T cells identified in two glioblastoma models using a cancer immunogenomics approach. Cancer Immunol. Res. 4, 1007\u20131015 (2016).","journal-title":"Cancer Immunol. Res."},{"key":"1330_CR43","doi-asserted-by":"publisher","first-page":"e006121","DOI":"10.1136\/jitc-2022-006121","volume":"11","author":"MO Schaettler","year":"2023","unstructured":"Schaettler, M. O. et al. TCR-engineered adoptive cell therapy effectively treats intracranial murine glioblastoma. J. Immunother. Cancer 11, e006121 (2023).","journal-title":"J. Immunother. Cancer"},{"key":"1330_CR44","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1038\/ni1102-991","volume":"3","author":"GP Dunn","year":"2002","unstructured":"Dunn, G. P., Bruce, A. T., Ikeda, H., Old, L. J. & Schreiber, R. D. Cancer immunoediting: from immunosurveillance to tumor escape. Nat. Immunol. 3, 991\u2013998 (2002).","journal-title":"Nat. Immunol."},{"key":"1330_CR45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/nyas.12105","volume":"1284","author":"MD Vesely","year":"2013","unstructured":"Vesely, M. D. & Schreiber, R. D. Cancer immunoediting: antigens, mechanisms, and implications to cancer immunotherapy: Tumor antigens and cancer immunoediting. Ann. N. Y. Acad. Sci. 1284, 1\u20135 (2013).","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"1330_CR46","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1038\/35074122","volume":"410","author":"V Shankaran","year":"2001","unstructured":"Shankaran, V. et al. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410, 1107\u20131111 (2001).","journal-title":"Nature"},{"key":"1330_CR47","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1084\/jem.184.5.1781","volume":"184","author":"ME van den Broek","year":"1996","unstructured":"van den Broek, M. E. et al. Decreased tumor surveillance in perforin-deficient mice. J. Exp. Med. 184, 1781\u20131790 (1996).","journal-title":"J. Exp. Med."},{"key":"1330_CR48","doi-asserted-by":"publisher","first-page":"7556","DOI":"10.1073\/pnas.95.13.7556","volume":"95","author":"DH Kaplan","year":"1998","unstructured":"Kaplan, D. H. et al. Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc. Natl. Acad. Sci. USA 95, 7556\u20137561 (1998).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"1330_CR49","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.trecan.2022.12.008","volume":"9","author":"MB Watowich","year":"2023","unstructured":"Watowich, M. B., Gilbert, M. R. & Larion, M. T cell exhaustion in malignant gliomas. Trends Cancer 9, 270\u2013292 (2023).","journal-title":"Trends Cancer"},{"key":"1330_CR50","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1146\/annurev-immunol-041015-055318","volume":"37","author":"LM McLane","year":"2019","unstructured":"McLane, L. M., Abdel-Hakeem, M. S. & Wherry, E. J. CD8 T cell exhaustion during chronic viral infection and cancer. Annu. Rev. Immunol. 37, 457\u2013495 (2019).","journal-title":"Annu. Rev. Immunol."},{"key":"1330_CR51","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1111\/j.1365-2567.2010.03255.x","volume":"129","author":"JS Yi","year":"2010","unstructured":"Yi, J. S., Cox, M. A. & Zajac, A. J. T-cell exhaustion: characteristics, causes and conversion: T-cell exhaustion. Immunology 129, 474\u2013481 (2010).","journal-title":"Immunology"},{"key":"1330_CR52","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1038\/ni.2035","volume":"12","author":"EJ Wherry","year":"2011","unstructured":"Wherry, E. J. T cell exhaustion. Nat. Immunol. 12, 492\u2013499 (2011).","journal-title":"Nat. Immunol."},{"key":"1330_CR53","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1016\/j.immuni.2020.04.014","volume":"52","author":"J-C Beltra","year":"2020","unstructured":"Beltra, J.-C. et al. Developmental relationships of four exhausted CD8+ T cell subsets reveals underlying transcriptional and epigenetic landscape control mechanisms. Immunity 52, 825\u2013841.e8 (2020).","journal-title":"Immunity"},{"key":"1330_CR54","doi-asserted-by":"publisher","first-page":"4175","DOI":"10.1158\/1078-0432.CCR-17-1846","volume":"24","author":"K Woroniecka","year":"2018","unstructured":"Woroniecka, K. et al. T-cell exhaustion signatures vary with tumor type and are severe in glioblastoma. Clin. Cancer Res. 24, 4175\u20134186 (2018).","journal-title":"Clin. Cancer Res."},{"key":"1330_CR55","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1038\/s41586-019-1326-9","volume":"571","author":"F Alfei","year":"2019","unstructured":"Alfei, F. et al. TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection. Nature 571, 265\u2013269 (2019).","journal-title":"Nature"},{"key":"1330_CR56","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1038\/nature05115","volume":"443","author":"CL Day","year":"2006","unstructured":"Day, C. L. et al. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 443, 350\u2013354 (2006).","journal-title":"Nature"},{"key":"1330_CR57","doi-asserted-by":"publisher","first-page":"11398","DOI":"10.1128\/JVI.01177-06","volume":"80","author":"S Urbani","year":"2006","unstructured":"Urbani, S. et al. PD-1 expression in acute hepatitis C virus (HCV) infection is associated with HCV-specific CD8 exhaustion. J. Virol. 80, 11398\u201311403 (2006).","journal-title":"J. Virol."},{"key":"1330_CR58","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1038\/ni.1679","volume":"10","author":"SD Blackburn","year":"2009","unstructured":"Blackburn, S. D. et al. Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat. Immunol. 10, 29\u201337 (2009).","journal-title":"Nat. Immunol."},{"key":"1330_CR59","doi-asserted-by":"publisher","first-page":"2569","DOI":"10.3389\/fimmu.2018.02569","volume":"9","author":"A Saeidi","year":"2018","unstructured":"Saeidi, A. et al. T-cell exhaustion in chronic infections: Reversing the state of exhaustion and reinvigorating optimal protective immune responses. Front. Immunol. 9, 2569 (2018).","journal-title":"Front. Immunol."},{"key":"1330_CR60","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abb9726","volume":"5","author":"G Escobar","year":"2020","unstructured":"Escobar, G., Mangani, D. & Anderson, A. C. T cell factor 1: A master regulator of the T cell response in disease. Sci. Immunol. 5, eabb9726 (2020).","journal-title":"Sci. Immunol."},{"key":"1330_CR61","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1016\/j.immuni.2019.09.013","volume":"51","author":"Z Chen","year":"2019","unstructured":"Chen, Z. et al. TCF-1-centered transcriptional network drives an effector versus exhausted CD8 T cell-fate decision. Immunity 51, 840\u2013855.e5 (2019).","journal-title":"Immunity"},{"key":"1330_CR62","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.immuni.2024.11.026","volume":"58","author":"J Waibl Polania","year":"2025","unstructured":"Waibl Polania, J. et al. Antigen presentation by tumor-associated macrophages drives T cells from a progenitor exhaustion state to terminal exhaustion. Immunity 58, 232\u2013246.e6 (2025).","journal-title":"Immunity"},{"key":"1330_CR63","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1016\/j.immuni.2019.11.002","volume":"51","author":"WH Hudson","year":"2019","unstructured":"Hudson, W. H. et al. Proliferating transitory T cells with an effector-like transcriptional signature emerge from PD-1+ stem-like CD8+ T cells during chronic infection. Immunity 51, 1043\u20131058.e4 (2019).","journal-title":"Immunity"},{"key":"1330_CR64","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/s41586-019-1836-5","volume":"576","author":"CS Jansen","year":"2019","unstructured":"Jansen, C. S. et al. An intra-tumoral niche maintains and differentiates stem-like CD8 T cells. Nature 576, 465\u2013470 (2019).","journal-title":"Nature"},{"key":"1330_CR65","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1038\/s41590-019-0312-6","volume":"20","author":"BC Miller","year":"2019","unstructured":"Miller, B. C. et al. Subsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade. Nat. Immunol. 20, 326\u2013336 (2019).","journal-title":"Nat. Immunol."},{"key":"1330_CR66","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.immuni.2022.12.002","volume":"56","author":"N Prokhnevska","year":"2023","unstructured":"Prokhnevska, N. et al. CD8+ T cell activation in cancer comprises an initial activation phase in lymph nodes followed by effector differentiation within the tumor. Immunity 56, 107\u2013124.e5 (2023).","journal-title":"Immunity"},{"key":"1330_CR67","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.add1016","volume":"15","author":"S Naulaerts","year":"2023","unstructured":"Naulaerts, S. et al. Multiomics and spatial mapping characterizes human CD8+ T cell states in cancer. Sci. Transl. Med. 15, eadd1016 (2023).","journal-title":"Sci. Transl. Med."},{"key":"1330_CR68","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1038\/s41568-019-0224-7","volume":"20","author":"JH Sampson","year":"2020","unstructured":"Sampson, J. H., Gunn, M. D., Fecci, P. E. & Ashley, D. M. Brain immunology and immunotherapy in brain tumours. Nat. Rev. Cancer 20, 12\u201325 (2020).","journal-title":"Nat. Rev. Cancer"},{"key":"1330_CR69","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1016\/j.ccell.2022.05.004","volume":"40","author":"K Kersten","year":"2022","unstructured":"Kersten, K. et al. Spatiotemporal co-dependency between macrophages and exhausted CD8+ T cells in cancer. Cancer Cell 40, 624\u2013638.e9 (2022).","journal-title":"Cancer Cell"},{"key":"1330_CR70","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1007\/s11060-020-03448-1","volume":"151","author":"R Medikonda","year":"2021","unstructured":"Medikonda, R., Dunn, G., Rahman, M., Fecci, P. & Lim, M. A review of glioblastoma immunotherapy. J. Neurooncol. 151, 41\u201353 (2021).","journal-title":"J. Neurooncol."},{"key":"1330_CR71","doi-asserted-by":"publisher","first-page":"e005293","DOI":"10.1136\/jitc-2022-005293","volume":"10","author":"SM Khan","year":"2022","unstructured":"Khan, S. M. et al. Impact of CD4 T cells on intratumoral CD8 T-cell exhaustion and responsiveness to PD-1 blockade therapy in mouse brain tumors. J. Immunother. Cancer 10, e005293 (2022).","journal-title":"J. Immunother. Cancer"},{"key":"1330_CR72","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.ccell.2022.12.007","volume":"41","author":"M Kilian","year":"2023","unstructured":"Kilian, M. et al. MHC class II-restricted antigen presentation is required to prevent dysfunction of cytotoxic T cells by blood-borne myeloids in brain tumors. Cancer Cell 41, 235\u2013251.e9 (2023).","journal-title":"Cancer Cell"},{"key":"1330_CR73","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14642-0","volume":"11","author":"K Aslan","year":"2020","unstructured":"Aslan, K. et al. Heterogeneity of response to immune checkpoint blockade in hypermutated experimental gliomas. Nat. Commun. 11, 931 (2020).","journal-title":"Nat. Commun."},{"key":"1330_CR74","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-015-0595-x","volume":"32","author":"X Jiang","year":"2015","unstructured":"Jiang, X. et al. The role of CD29-ILK-Akt signaling-mediated epithelial-mesenchymal transition of liver epithelial cells and chemoresistance and radioresistance in hepatocellular carcinoma cells. Med. Oncol. 32, 141 (2015).","journal-title":"Med. Oncol."},{"key":"1330_CR75","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.cellsig.2009.10.003","volume":"22","author":"AE Saunders","year":"2010","unstructured":"Saunders, A. E. & Johnson, P. Modulation of immune cell signalling by the leukocyte common tyrosine phosphatase, CD45. Cell. Signal. 22, 339\u2013348 (2010).","journal-title":"Cell. Signal."},{"key":"1330_CR76","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-56102-5","volume":"14","author":"VJ Marallano","year":"2024","unstructured":"Marallano, V. J. et al. Hypoxia drives shared and distinct transcriptomic changes in two invasive glioma stem cell lines. Sci. Rep. 14, 7246 (2024).","journal-title":"Sci. Rep."},{"key":"1330_CR77","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1093\/neuonc\/now258","volume":"19","author":"N Colwell","year":"2017","unstructured":"Colwell, N. et al. Hypoxia in the glioblastoma microenvironment: shaping the phenotype of cancer stem-like cells. Neuro. Oncol. 19, 887\u2013896 (2017).","journal-title":"Neuro. Oncol."},{"key":"1330_CR78","doi-asserted-by":"crossref","unstructured":"Monteiro, A. R., Hill, R., Pilkington, G. J. & Madureira, P. A. The role of hypoxia in glioblastoma invasion. Cells 6, 45 (2017).","DOI":"10.3390\/cells6040045"},{"key":"1330_CR79","doi-asserted-by":"publisher","first-page":"12608","DOI":"10.3390\/ijms222212608","volume":"22","author":"M Dom\u00e8nech","year":"2021","unstructured":"Dom\u00e8nech, M., Hern\u00e1ndez, A., Plaja, A., Mart\u00ednez-Balibrea, E. & Bala\u00f1\u00e0, C. Hypoxia: the cornerstone of glioblastoma. Int. J. Mol. Sci. 22, 12608 (2021).","journal-title":"Int. J. Mol. Sci."},{"key":"1330_CR80","doi-asserted-by":"publisher","first-page":"3052","DOI":"10.1007\/s10528-023-10597-1","volume":"62","author":"X Cai","year":"2024","unstructured":"Cai, X. et al. Profiling and bioinformatics analyses of hypoxia-induced differential expression of long non-coding RNA in glioblastoma multiforme cells. Biochem. Genet. 62, 3052\u20133070 (2024).","journal-title":"Biochem. Genet."},{"key":"1330_CR81","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1016\/j.cell.2013.05.016","volume":"153","author":"C-H Chang","year":"2013","unstructured":"Chang, C.-H. et al. Posttranscriptional control of T cell effector function by aerobic glycolysis. Cell 153, 1239\u20131251 (2013).","journal-title":"Cell"},{"key":"1330_CR82","doi-asserted-by":"publisher","first-page":"5518","DOI":"10.3390\/ijms22115518","volume":"22","author":"AM Reuss","year":"2021","unstructured":"Reuss, A. M., Groos, D., Buchfelder, M. & Savaskan, N. The acidic brain-glycolytic switch in the microenvironment of malignant glioma. Int. J. Mol. Sci. 22, 5518 (2021).","journal-title":"Int. J. Mol. Sci."},{"key":"1330_CR83","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","volume":"144","author":"D Hanahan","year":"2011","unstructured":"Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646\u2013674 (2011).","journal-title":"Cell"},{"key":"1330_CR84","doi-asserted-by":"publisher","first-page":"3061","DOI":"10.1016\/j.molcel.2022.06.030","volume":"82","author":"C Torrini","year":"2022","unstructured":"Torrini, C. et al. Lactate is an epigenetic metabolite that drives survival in model systems of glioblastoma. Mol. Cell 82, 3061\u20133076.e6 (2022).","journal-title":"Mol. Cell"},{"key":"1330_CR85","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.4161\/cbt.8.14.8882","volume":"8","author":"R Li","year":"2009","unstructured":"Li, R. et al. IDO inhibits T-cell function through suppressing Vav1 expression and activation. Cancer Biol. Ther. 8, 1402\u20131408 (2009).","journal-title":"Cancer Biol. Ther."},{"key":"1330_CR86","doi-asserted-by":"publisher","first-page":"6650","DOI":"10.1158\/1078-0432.CCR-17-0120","volume":"23","author":"L Zhai","year":"2017","unstructured":"Zhai, L. et al. Infiltrating T cells increase IDO1 expression in glioblastoma and contribute to decreased patient survival. Clin. Cancer Res. 23, 6650\u20136660 (2017).","journal-title":"Clin. Cancer Res."},{"key":"1330_CR87","doi-asserted-by":"publisher","first-page":"6110","DOI":"10.1158\/1078-0432.CCR-12-2130","volume":"18","author":"DA Wainwright","year":"2012","unstructured":"Wainwright, D. A. et al. IDO expression in brain tumors increases the recruitment of regulatory T cells and negatively impacts survival. Clin. Cancer Res. 18, 6110\u20136121 (2012).","journal-title":"Clin. Cancer Res."},{"key":"1330_CR88","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1007\/s11060-014-1687-8","volume":"123","author":"L Zhai","year":"2015","unstructured":"Zhai, L. et al. The role of IDO in brain tumor immunotherapy. J. Neurooncol. 123, 395\u2013403 (2015).","journal-title":"J. Neurooncol."},{"key":"1330_CR89","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1038\/s43018-021-00201-z","volume":"2","author":"M Friedrich","year":"2021","unstructured":"Friedrich, M. et al. Tryptophan metabolism drives dynamic immunosuppressive myeloid states in IDH-mutant gliomas. Nat. Cancer 2, 723\u2013740 (2021).","journal-title":"Nat. Cancer"},{"key":"1330_CR90","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1158\/2159-8290.CD-23-0913","volume":"14","author":"AZ Wang","year":"2024","unstructured":"Wang, A. Z. et al. Glioblastoma-infiltrating CD8+ T cells are predominantly a clonally expanded GZMK+ effector population. Cancer Discov. 14, 1106\u20131131 (2024).","journal-title":"Cancer Discov."},{"key":"1330_CR91","doi-asserted-by":"publisher","first-page":"2090","DOI":"10.1158\/2159-8290.CD-22-0869","volume":"13","author":"J Lee","year":"2023","unstructured":"Lee, J. et al. Sex-biased T-cell exhaustion drives differential immune responses in glioblastoma. Cancer Discov. 13, 2090\u20132105 (2023).","journal-title":"Cancer Discov."},{"key":"1330_CR92","doi-asserted-by":"crossref","unstructured":"Yamada, T. et al. Lenvatinib recruits cytotoxic GZMK+CD8 T cells in hepatocellular carcinoma. Hepatol. Commun 7, (2023).","DOI":"10.1097\/HC9.0000000000000209"},{"key":"1330_CR93","doi-asserted-by":"crossref","unstructured":"Masuda, K. et al. Multiplexed single-cell analysis reveals prognostic and nonprognostic T cell types in human colorectal cancer. JCI Insight. 7, (2022).","DOI":"10.1172\/jci.insight.154646"},{"key":"1330_CR94","doi-asserted-by":"publisher","first-page":"1358","DOI":"10.1016\/j.ccell.2022.10.017","volume":"40","author":"R Sklavenitis-Pistofidis","year":"2022","unstructured":"Sklavenitis-Pistofidis, R. et al. Immune biomarkers of response to immunotherapy in patients with high-risk smoldering myeloma. Cancer Cell 40, 1358\u20131373.e8 (2022).","journal-title":"Cancer Cell"},{"key":"1330_CR95","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1016\/j.ccell.2021.10.001","volume":"39","author":"L Au","year":"2021","unstructured":"Au, L. et al. Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma. Cancer Cell 39, 1497\u20131518.e11 (2021).","journal-title":"Cancer Cell"},{"key":"1330_CR96","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1038\/s43018-021-00292-8","volume":"3","author":"B Liu","year":"2022","unstructured":"Liu, B. et al. Temporal single-cell tracing reveals clonal revival and expansion of precursor exhausted T cells during anti-PD-1 therapy in lung cancer. Nat. Cancer 3, 108\u2013121 (2022).","journal-title":"Nat. Cancer"},{"key":"1330_CR97","doi-asserted-by":"publisher","first-page":"2330","DOI":"10.1158\/2159-8290.CD-21-1248","volume":"12","author":"A Schalck","year":"2022","unstructured":"Schalck, A. et al. Single-cell sequencing reveals trajectory of tumor-infiltrating lymphocyte states in pancreatic cancer. Cancer Discov. 12, 2330\u20132349 (2022).","journal-title":"Cancer Discov."},{"key":"1330_CR98","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1038\/s41586-024-08395-9","volume":"638","author":"F Lan","year":"2025","unstructured":"Lan, F. et al. GZMK-expressing CD8+ T cells promote recurrent airway inflammatory diseases. Nature 638, 490\u2013498 (2025).","journal-title":"Nature"},{"key":"1330_CR99","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/s41586-025-08713-9","volume":"641","author":"CA Donado","year":"2025","unstructured":"Donado, C. A. et al. Granzyme K activates the entire complement cascade. Nature 641, 211\u2013221 (2025).","journal-title":"Nature"},{"key":"1330_CR100","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/nri.2017.97","volume":"18","author":"ES Reis","year":"2018","unstructured":"Reis, E. S., Mastellos, D. C., Ricklin, D., Mantovani, A. & Lambris, J. D. Complement in cancer: untangling an intricate relationship. Nat. Rev. Immunol. 18, 5\u201318 (2018).","journal-title":"Nat. Rev. Immunol."},{"key":"1330_CR101","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1002\/cam4.241","volume":"3","author":"ET Sayegh","year":"2014","unstructured":"Sayegh, E. T., Bloch, O. & Parsa, A. T. Complement anaphylatoxins as immune regulators in cancer. Cancer Med. 3, 747\u2013758 (2014).","journal-title":"Cancer Med."},{"key":"1330_CR102","doi-asserted-by":"publisher","first-page":"4674","DOI":"10.4049\/jimmunol.1201654","volume":"189","author":"L Corrales","year":"2012","unstructured":"Corrales, L. et al. Anaphylatoxin C5a creates a favorable microenvironment for lung cancer progression. J. Immunol. 189, 4674\u20134683 (2012).","journal-title":"J. Immunol."},{"key":"1330_CR103","doi-asserted-by":"publisher","first-page":"1297932","DOI":"10.3389\/fimmu.2023.1297932","volume":"14","author":"JB Iorgulescu","year":"2023","unstructured":"Iorgulescu, J. B. et al. Antigen presentation deficiency, mesenchymal differentiation, and resistance to immunotherapy in the murine syngeneic CT2A tumor model. Front. Immunol. 14, 1297932 (2023).","journal-title":"Front. Immunol."},{"key":"1330_CR104","doi-asserted-by":"publisher","first-page":"4685","DOI":"10.1158\/1078-0432.CCR-21-0327","volume":"27","author":"L Marcus","year":"2021","unstructured":"Marcus, L. et al. FDA approval summary: Pembrolizumab for the treatment of tumor mutational burden-high solid tumors. Clin. Cancer Res. 27, 4685\u20134689 (2021).","journal-title":"Clin. Cancer Res."},{"key":"1330_CR105","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1038\/nature12477","volume":"500","author":"LB Alexandrov","year":"2013","unstructured":"Alexandrov, L. B. et al. Signatures of mutational processes in human cancer. Nature 500, 415\u2013421 (2013).","journal-title":"Nature"},{"key":"1330_CR106","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1016\/j.cell.2013.09.034","volume":"155","author":"CW Brennan","year":"2013","unstructured":"Brennan, C. W. et al. The somatic genomic landscape of glioblastoma. Cell 155, 462\u2013477 (2013).","journal-title":"Cell"},{"key":"1330_CR107","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1038\/s41586-018-0810-y","volume":"565","author":"N Hilf","year":"2019","unstructured":"Hilf, N. et al. Actively personalized vaccination trial for newly diagnosed glioblastoma. Nature 565, 240\u2013245 (2019).","journal-title":"Nature"},{"key":"1330_CR108","doi-asserted-by":"publisher","first-page":"e1501137","DOI":"10.1080\/2162402X.2018.1501137","volume":"7","author":"V Genoud","year":"2018","unstructured":"Genoud, V. et al. Responsiveness to anti-PD-1 and anti-CTLA-4 immune checkpoint blockade in SB28 and GL261 mouse glioma models. Oncoimmunology 7, e1501137 (2018).","journal-title":"Oncoimmunology"},{"key":"1330_CR109","doi-asserted-by":"publisher","first-page":"6697","DOI":"10.4049\/jimmunol.0800997","volume":"182","author":"CM Bucks","year":"2009","unstructured":"Bucks, C. M., Norton, J. A., Boesteanu, A. C., Mueller, Y. M. & Katsikis, P. D. Chronic antigen stimulation alone is sufficient to drive CD8+ T cell exhaustion. J. Immunol. 182, 6697\u20136708 (2009).","journal-title":"J. Immunol."},{"key":"1330_CR110","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1038\/s41591-019-0522-3","volume":"25","author":"KE Yost","year":"2019","unstructured":"Yost, K. E. et al. Clonal replacement of tumor-specific T cells following PD-1 blockade. Nat. Med. 25, 1251\u20131259 (2019).","journal-title":"Nat. Med."},{"key":"1330_CR111","doi-asserted-by":"crossref","unstructured":"Arrieta, V. A. et al. Immune checkpoint blockade in glioblastoma: from tumor heterogeneity to personalized treatment. J. Clin. Investig. 133, e163447 (2023).","DOI":"10.1172\/JCI163447"},{"key":"1330_CR112","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1093\/neuonc\/noac099","volume":"25","author":"A Omuro","year":"2023","unstructured":"Omuro, A. et al. Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: an international randomized phase III trial. Neuro. Oncol. 25, 123\u2013134 (2023).","journal-title":"Neuro. Oncol."},{"key":"1330_CR113","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.162","volume":"6","author":"Y Jiang","year":"2015","unstructured":"Jiang, Y., Li, Y. & Zhu, B. T-cell exhaustion in the tumor microenvironment. Cell Death Dis. 6, e1792 (2015).","journal-title":"Cell Death Dis."},{"key":"1330_CR114","doi-asserted-by":"publisher","first-page":"e002780","DOI":"10.1136\/jitc-2021-002780","volume":"9","author":"CG Kim","year":"2021","unstructured":"Kim, C. G. et al. Distinct exhaustion features of T lymphocytes shape the tumor-immune microenvironment with therapeutic implication in patients with non-small-cell lung cancer. J. Immunother. Cancer 9, e002780 (2021).","journal-title":"J. Immunother. Cancer"},{"key":"1330_CR115","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-017-0424-2","volume":"9","author":"ZR Chalmers","year":"2017","unstructured":"Chalmers, Z. R. et al. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med 9, 34 (2017).","journal-title":"Genome Med"},{"key":"1330_CR116","doi-asserted-by":"publisher","first-page":"3044","DOI":"10.3390\/curroncol29050247","volume":"29","author":"Y Shiravand","year":"2022","unstructured":"Shiravand, Y. et al. Immune checkpoint inhibitors in cancer therapy. Curr. Oncol. 29, 3044\u20133060 (2022).","journal-title":"Curr. Oncol."},{"key":"1330_CR117","doi-asserted-by":"publisher","DOI":"10.1200\/PO.23.00092","volume":"7","author":"JCF Quintanilha","year":"2023","unstructured":"Quintanilha, J. C. F. et al. Tumor mutational burden in real-world patients with pancreatic cancer: Genomic alterations and predictive value for immune checkpoint inhibitor effectiveness. JCO Precis. Oncol. 7, e2300092 (2023).","journal-title":"JCO Precis. Oncol."},{"key":"1330_CR118","doi-asserted-by":"publisher","first-page":"3537","DOI":"10.21873\/anticanres.15840","volume":"42","author":"Y Akiyama","year":"2022","unstructured":"Akiyama, Y. et al. Characterization of the immunological status of hypermutated solid tumors in the Cancer Genome Analysis Project HOPE. Anticancer Res 42, 3537\u20133549 (2022).","journal-title":"Anticancer Res"},{"key":"1330_CR119","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1038\/s41591-018-0057-z","volume":"24","author":"DS Thommen","year":"2018","unstructured":"Thommen, D. S. et al. A transcriptionally and functionally distinct PD-1+ CD8+ T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade. Nat. Med. 24, 994\u20131004 (2018).","journal-title":"Nat. Med."},{"key":"1330_CR120","doi-asserted-by":"publisher","first-page":"2206","DOI":"10.1200\/JCO.2016.66.6552","volume":"34","author":"E Bouffet","year":"2016","unstructured":"Bouffet, E. et al. Immune checkpoint inhibition for hypermutant glioblastoma multiforme resulting from germline biallelic mismatch repair deficiency. J. Clin. Oncol. 34, 2206\u20132211 (2016).","journal-title":"J. Clin. Oncol."},{"key":"1330_CR121","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1158\/2159-8290.CD-16-0575","volume":"6","author":"TM Johanns","year":"2016","unstructured":"Johanns, T. M. et al. Immunogenomics of hypermutated glioblastoma: a patient with germline POLE deficiency treated with checkpoint blockade immunotherapy. Cancer Discov. 6, 1230\u20131236 (2016).","journal-title":"Cancer Discov."},{"key":"1330_CR122","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1038\/s41586-020-2209-9","volume":"580","author":"M Touat","year":"2020","unstructured":"Touat, M. et al. Mechanisms and therapeutic implications of hypermutation in gliomas. Nature 580, 517\u2013523 (2020).","journal-title":"Nature"},{"key":"1330_CR123","doi-asserted-by":"publisher","first-page":"E2776","DOI":"10.1073\/pnas.1620498114","volume":"114","author":"GP Mognol","year":"2017","unstructured":"Mognol, G. P. et al. Exhaustion-associated regulatory regions in CD8+ tumor-infiltrating T cells. Proc. Natl. Acad. Sci. USA 114, E2776\u2013E2785 (2017).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"1330_CR124","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41586-019-1324-y","volume":"571","author":"AC Scott","year":"2019","unstructured":"Scott, A. C. et al. TOX is a critical regulator of tumour-specific T cell differentiation. Nature 571, 270\u2013274 (2019).","journal-title":"Nature"},{"key":"1330_CR125","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/j.immuni.2016.07.011","volume":"45","author":"A Schietinger","year":"2016","unstructured":"Schietinger, A. et al. Tumor-specific T cell dysfunction is a dynamic antigen-driven differentiation program initiated early during tumorigenesis. Immunity 45, 389\u2013401 (2016).","journal-title":"Immunity"},{"key":"1330_CR126","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-024-00753-0","volume":"8","author":"S Park","year":"2024","unstructured":"Park, S., Maus, M. V. & Choi, B. D. CAR-T cell therapy for the treatment of adult high-grade gliomas. NPJ Precis. Oncol. 8, 279 (2024).","journal-title":"NPJ Precis. Oncol."},{"key":"1330_CR127","doi-asserted-by":"publisher","first-page":"2113","DOI":"10.1056\/NEJMoa2210233","volume":"387","author":"MW Rohaan","year":"2022","unstructured":"Rohaan, M. W. et al. Tumor-infiltrating lymphocyte therapy or ipilimumab in advanced melanoma. N. Engl. J. Med. 387, 2113\u20132125 (2022).","journal-title":"N. Engl. J. Med."},{"key":"1330_CR128","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1093\/oncolo\/oyae136","volume":"29","author":"MLM Kwong","year":"2024","unstructured":"Kwong, M. L. M. & Yang, J. C. Lifileucel: FDA-approved T-cell therapy for melanoma. Oncologist 29, 648\u2013650 (2024).","journal-title":"Oncologist"},{"key":"1330_CR129","doi-asserted-by":"publisher","first-page":"2656","DOI":"10.1200\/JCO.21.00612","volume":"39","author":"AA Sarnaik","year":"2021","unstructured":"Sarnaik, A. A. et al. Lifileucel, a tumor-infiltrating lymphocyte therapy, in metastatic melanoma. J. Clin. Oncol. 39, 2656\u20132666 (2021).","journal-title":"J. Clin. Oncol."},{"key":"1330_CR130","doi-asserted-by":"publisher","first-page":"2042","DOI":"10.1200\/JCO.2023.41.16_suppl.2042","volume":"41","author":"Y Yao","year":"2023","unstructured":"Yao, Y. et al. Safety, efficacy, and biomarker analysis of response to engineered tumor-infiltrating lymphocytes secreting anti-PD-1 antibody in recurrent glioblastoma: an open-label, two-arms, phase 1 study. J. Clin. Oncol. 41, 2042 (2023).","journal-title":"J. Clin. Oncol."},{"key":"1330_CR131","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/nature22991","volume":"547","author":"PA Ott","year":"2017","unstructured":"Ott, P. A. et al. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature 547, 217\u2013221 (2017).","journal-title":"Nature"},{"key":"1330_CR132","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1038\/s41591-020-01206-4","volume":"27","author":"Z Hu","year":"2021","unstructured":"Hu, Z. et al. Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma. Nat. Med. 27, 515\u2013525 (2021).","journal-title":"Nat. Med."},{"key":"1330_CR133","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.cell.2020.08.053","volume":"183","author":"PA Ott","year":"2020","unstructured":"Ott, P. A. et al. A phase Ib trial of personalized neoantigen therapy plus anti-PD-1 in patients with advanced melanoma, non-small cell lung cancer, or bladder cancer. Cell 183, 347\u2013362.e24 (2020).","journal-title":"Cell"},{"key":"1330_CR134","doi-asserted-by":"publisher","first-page":"114312","DOI":"10.1016\/j.addr.2022.114312","volume":"186","author":"GP Dunn","year":"2022","unstructured":"Dunn, G. P., Sherpa, N., Manyanga, J. & Johanns, T. M. Considerations for personalized neoantigen vaccination in Malignant glioma. Adv. Drug Deliv. Rev. 186, 114312 (2022).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"1330_CR135","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1093\/neuros\/nyx321","volume":"64","author":"TM Johanns","year":"2017","unstructured":"Johanns, T. M., Bowman-Kirigin, J. A., Liu, C. & Dunn, G. P. Targeting neoantigens in glioblastoma: An overview of cancer immunogenomics and translational implications. Neurosurgery 64, 165\u2013176 (2017).","journal-title":"Neurosurgery"},{"key":"1330_CR136","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1097\/PPO.0000000000000247","volume":"23","author":"TM Johanns","year":"2017","unstructured":"Johanns, T. M. & Dunn, G. P. Applied cancer immunogenomics: Leveraging neoantigen discovery in glioblastoma. Cancer J. 23, 125\u2013130 (2017).","journal-title":"Cancer J."},{"key":"1330_CR137","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-51315-8","volume":"15","author":"P Latzer","year":"2024","unstructured":"Latzer, P. et al. A real-world observation of patients with glioblastoma treated with a personalized peptide vaccine. Nat. Commun. 15, 6870 (2024).","journal-title":"Nat. Commun."},{"key":"1330_CR138","doi-asserted-by":"publisher","first-page":"2586","DOI":"10.1038\/s41591-023-02555-6","volume":"29","author":"N Grassl","year":"2023","unstructured":"Grassl, N. et al. A H3K27M-targeted vaccine in adults with diffuse midline glioma. Nat. Med. 29, 2586\u20132592 (2023).","journal-title":"Nat. Med."},{"key":"1330_CR139","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1038\/s41587-024-02435-5","volume":"42","author":"C Harrison","year":"2024","unstructured":"Harrison, C. TCR cell therapies vanquish solid tumors-finally. Nat. Biotechnol. 42, 1477\u20131479 (2024).","journal-title":"Nat. Biotechnol."},{"key":"1330_CR140","doi-asserted-by":"publisher","first-page":"2256","DOI":"10.1056\/NEJMoa2304753","volume":"389","author":"JC Hassel","year":"2023","unstructured":"Hassel, J. C. et al. Three-year overall survival with tebentafusp in metastatic uveal melanoma. N. Engl. J. Med. 389, 2256\u20132266 (2023).","journal-title":"N. Engl. J. Med."},{"key":"1330_CR141","unstructured":"TECELRA (afamitresgene autoleucel) Patient Website https:\/\/www.tecelra.com\/."},{"key":"1330_CR142","unstructured":"KIMMTRAK\u00ae (tebentafusp-tebn)-official website https:\/\/www.kimmtrak.com\/."},{"key":"1330_CR143","doi-asserted-by":"publisher","first-page":"1387","DOI":"10.1126\/science.aad1253","volume":"350","author":"E Tran","year":"2015","unstructured":"Tran, E. et al. Immunogenicity of somatic mutations in human gastrointestinal cancers. Science 350, 1387\u20131390 (2015).","journal-title":"Science"},{"key":"1330_CR144","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/s41586-018-0792-9","volume":"565","author":"DB Keskin","year":"2019","unstructured":"Keskin, D. B. et al. Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature 565, 234\u2013239 (2019).","journal-title":"Nature"},{"key":"1330_CR145","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1126\/science.abl5447","volume":"375","author":"FJ Lowery","year":"2022","unstructured":"Lowery, F. J. et al. Molecular signatures of antitumor neoantigen-reactive T cells from metastatic human cancers. Science 375, 877\u2013884 (2022).","journal-title":"Science"},{"key":"1330_CR146","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1038\/s41587-024-02161-y","volume":"43","author":"CL Tan","year":"2025","unstructured":"Tan, C. L. et al. Prediction of tumor-reactive T cell receptors from scRNA-seq data for personalized T cell therapy. Nat. Biotechnol. 43, 134\u2013142 (2025).","journal-title":"Nat. Biotechnol."},{"key":"1330_CR147","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1038\/s41586-021-03704-y","volume":"596","author":"G Oliveira","year":"2021","unstructured":"Oliveira, G. et al. Phenotype, specificity and avidity of antitumour CD8+ T cells in melanoma. Nature 596, 119\u2013125 (2021).","journal-title":"Nature"},{"key":"1330_CR148","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1016\/j.ccell.2022.03.012","volume":"40","author":"K-I Hanada","year":"2022","unstructured":"Hanada, K.-I. et al. A phenotypic signature that identifies neoantigen-reactive T cells in fresh human lung cancers. Cancer Cell 40, 479\u2013493.e6 (2022).","journal-title":"Cancer Cell"},{"key":"1330_CR149","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1093\/neuonc\/noaa050","volume":"22","author":"CJ Liu","year":"2020","unstructured":"Liu, C. J. et al. Treatment of an aggressive orthotopic murine glioblastoma model with combination checkpoint blockade and a multivalent neoantigen vaccine. Neuro. Oncol. 22, 1276\u20131288 (2020).","journal-title":"Neuro. Oncol."}],"container-title":["npj Precision Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41698-026-01330-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41698-026-01330-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41698-026-01330-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:02:16Z","timestamp":1783900936000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41698-026-01330-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,13]]},"references-count":149,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1330"],"URL":"https:\/\/doi.org\/10.1038\/s41698-026-01330-3","relation":{},"ISSN":["2397-768X"],"issn-type":[{"value":"2397-768X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,13]]},"assertion":[{"value":"28 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"274"}}