{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T06:06:44Z","timestamp":1784700404187,"version":"3.55.0"},"reference-count":145,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"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>Glioblastoma (GB) remains one of the most aggressive brain tumours, with a median survival of 15 months, largely due to resistance towards available anti-cancer therapies, including cutting-edge immunotherapy. Growing evidence indicates involvement of cancer stem cells (CSCs) in escalating resistance against existing treatment modalities due to their phenotypic plasticity, elevated expression of drug-resistance pumps, and immunomodulatory behaviour. Such oncogenic consequences are regulated by several epigenetic reprogramming events that are pivotal in retaining adaptive traits associated with CSC-mediated therapy resistance and subsequent oncogenic progression. In this review, we consider such epigenetic consequences as \u201ctumour memory\u201d and try to shed light on the therapeutic vulnerabilities by targeting CSCs \u2014 the \u201ccarriers of tumour memory\u201d \u2014 via immune interventions in GB. Interestingly, immune-based anti-cancer therapies are coming to the forefront of cancer research, where T lymphocytes are immunologically boosted to attack tumour cells. However, in reality, several constraints burden such procedures. Contextually, the GB microenvironment, dominated by bone marrow-derived cells, reprograms infiltrating immune cells into suppressor phenotypes, creating a \u201ccold\u201d immune landscape. The only zone where functionally active lymphocytes are preserved is the invasive margin of the tumour, where they undergo exhaustion along the TPE \u2192 TEX axis but retain proliferative potential. On this basis, we introduce the concept of \u201cinvasive margin lymphocytes\u201d (IMLs), of which stem-like memory T cells (TSCM) are indispensable for long-term immunological protection, as they have unique proliferative potential and ability for long-term persistence. Incidentally, such TSCMs have striking similarities with CSCs, as both cell types employ evolutionarily conserved mechanisms of the WNT\/\u03b2-catenin signalling pathway, hierarchical organisation, and DNA repair systems. Therefore, understanding CSC\u2013TSCM bidirectional cross-talk could provide a heuristic basis for developing personalised TIL-based therapy aimed at suppressing the hierarchically organised CSC population and overcoming CSC-guided immunotherapy resistance. Drawing conceptual parallels between GB CSCs and TSCM, here in this review, we propose a three-stage therapeutic strategy: precision cytoreduction of the invasive margin, \u201cwarming up\u201d the microenvironment using cancer vaccines and pharmacological agents, as well as adoptive transfer of TILs derived from the IML pool to ensure durable disease control.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1880908","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:53:38Z","timestamp":1784699618000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Glioblastoma stem cells as carriers of tumour memory: a strategy for personalised immunotherapy using tumour-infiltrating lymphocytes"],"prefix":"10.3389","volume":"17","author":[{"given":"Igor","family":"Bryukhovetskiy","sequence":"first","affiliation":[{"name":"Far Eastern Federal University Hospital","place":["Vladivostok, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg","family":"Pak","sequence":"additional","affiliation":[{"name":"Far Eastern Federal University Hospital","place":["Vladivostok, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Polevshchikov","sequence":"additional","affiliation":[{"name":"Laboratory of General Immunology, Institute of Experimental Medicine","place":["Saint-Petersburg, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1093\/neuonc\/noaf217","article-title":"EANS-EANO guidelines on the extent of resection in gliomas","volume":"28","author":"Goldbrunner","year":"2026","journal-title":"Neuro Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI163446","article-title":"Macrophages and microglia in glioblastoma: heterogeneity, plasticity, and therapy","volume":"133","author":"Khan","year":"2023","journal-title":"J Clin Invest"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1101\/gad.351427.123","article-title":"Glioblastoma microenvironment-from biology to therapy","volume":"38","author":"Read","year":"2024","journal-title":"Genes Dev"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24087047","article-title":"Glioblastoma microenvironment and invasiveness: new insights and therapeutic targets","volume":"24","author":"Erices","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2022.153813","article-title":"Glioblastoma microenvironment: the stromal interactions","volume":"232","author":"Uyar","year":"2022","journal-title":"Pathol Res Pract"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1126\/science.abm5214","article-title":"Distinct myeloid-derived suppressor cell populations in human glioblastoma","volume":"387","author":"Jackson","year":"2025","journal-title":"Science"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1472710","article-title":"Rational therapeutic targeting of myeloid cells in glioblastoma: challenges and perspectives","volume":"16","author":"Akay","year":"2025","journal-title":"Front Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-23-0913","article-title":"Glioblastoma-infiltrating CD8+ T cells are predominantly a clonally expanded GZMK+ effector population","volume":"14","author":"Wang","year":"2024","journal-title":"Cancer Discov"},{"key":"B9","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1007\/s11033-026-11525-3","article-title":"Neutrophils in glioblastoma: orchestrators of the tumor microenvironment and immune evasion","volume":"53","author":"Demir","year":"2026","journal-title":"Mol Biol Rep"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-24-0807","article-title":"The TRIB2-DNMT1 pathway generates an immune-cold microenvironment in glioblastoma, and its inhibition promotes immunotherapy","volume":"13","author":"Segura-Collar","year":"2025","journal-title":"Cancer Immunol Res"},{"key":"B11","doi-asserted-by":"publisher","first-page":"24","DOI":"10.3892\/br.2023.1712","article-title":"Regulation of cancer stem cells and immunotherapy of glioblastoma (review)","volume":"20","author":"Kosianova","year":"2023","journal-title":"BioMed Rep"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-024-10183-w","article-title":"Glioblastoma stem cell metabolism and immunity","volume":"43","author":"Hawly","year":"2024","journal-title":"Cancer Metastasis Rev"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3233\/CBM-230486","article-title":"Glioma stem cells remodel immunotolerant microenvironment in GBM and are associated with therapeutic advancements","volume":"41","author":"Fei","year":"2024","journal-title":"Cancer biomark"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s00701-020-04605-1","article-title":"Primary versus recurrent surgery for glioblastoma-a prospective cohort study","volume":"164","author":"Rubin","year":"2022","journal-title":"Acta Neurochir (Wien)"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noac193","article-title":"Prognostic validation of a new classification system for extent of resection in glioblastoma: a report of the RANO resect group","volume":"25","author":"Karschnia","year":"2023","journal-title":"Neuro Oncol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-1846","article-title":"T-cell exhaustion signatures vary with tumor type and are severe in glioblastoma","volume":"24","author":"Woroniecka","year":"2018","journal-title":"Clin Cancer Res"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1325-x","article-title":"TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion","volume":"571","author":"Khan","year":"2019","journal-title":"Nature"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043330","article-title":"Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma","volume":"352","author":"Stupp","year":"2005","journal-title":"N Engl J Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3390\/ijms262412162","article-title":"Glioblastoma-a contemporary overview of epidemiology, classification, pathogenesis, diagnosis, and treatment: a review article","volume":"26","author":"Krolikowska","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.533000","article-title":"Influence of intratumor heterogeneity on the predictivity of MGMT gene promoter methylation status in glioblastoma","volume":"10","author":"Brigliadori","year":"2020","journal-title":"Front Oncol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15174279","article-title":"Recurrent glioblastoma: a review of the treatment options","volume":"15","author":"Vaz-Salgado","year":"2023","journal-title":"Cancers (Basel)"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2020.106343","article-title":"The merits of awake craniotomy for glioblastoma in the left hemispheric eloquent area: one institution experience","volume":"200","author":"Li","year":"2021","journal-title":"Clin Neurol Neurosurg"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(22)00213-3","article-title":"Effect of awake craniotomy in glioblastoma in eloquent areas (GLIOMAP): a propensity score-matched analysis of an international, multicentre, cohort study","volume":"23","author":"Gerritsen","year":"2022","journal-title":"Lancet Oncol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noab269","article-title":"Cancer cell heterogeneity and plasticity: a paradigm shift in glioblastoma","volume":"24","author":"Yabo","year":"2022","journal-title":"Neuro Oncol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.17179\/excli2024-6972","article-title":"Plasticity and resistance of cancer stem cells as a challenge for innovative anticancer therapies - do we know enough to overcome this","volume":"23","author":"Knopik-Skrocka","year":"2024","journal-title":"EXCLI J"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2023.03.013","article-title":"Overcoming the blood brain barrier in glioblastoma: status and future perspective","volume":"179","author":"Ahmed","year":"2023","journal-title":"Rev Neurol (Paris)"},{"key":"B27","doi-asserted-by":"publisher","first-page":"3089","DOI":"10.1016\/j.neuron.2024.07.026","article-title":"Single-cell dissection of the human blood-brain barrier and glioma blood-tumor barrier","volume":"112","author":"Xie","year":"2024","journal-title":"Neuron"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-022-04144-y","article-title":"Postmortem study of organ-specific toxicity in glioblastoma patients treated with a combination of temozolomide, irinotecan and bevacizumab","volume":"160","author":"Lu","year":"2022","journal-title":"J Neuro-Oncol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-03-0807","article-title":"Plasma and cerebrospinal fluid population pharmacokinetics of temozolomide in Malignant glioma patients","volume":"10","author":"Ostermann","year":"2004","journal-title":"Clin Cancer Res"},{"key":"B30","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1186\/s12885-025-13757-1","article-title":"The role of temozolomide as adjuvant therapy in glioblastoma management: a systematic review and meta-analysis","volume":"25","author":"Inggas","year":"2025","journal-title":"BMC Cancer"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3390\/cancers18050860","article-title":"Translating molecular insights into effective targeting of glioblastoma stem cells","volume":"18","author":"Singh","year":"2026","journal-title":"Cancers (Basel)"},{"key":"B32","doi-asserted-by":"publisher","first-page":"10905","DOI":"10.1038\/s41467-025-65888-5","article-title":"Histone methyltransferase PRDM9 promotes survival of drug-tolerant persister cells in glioblastoma","volume":"16","author":"Joun","year":"2025","journal-title":"Nat Commun"},{"key":"B33","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.stem.2016.11.003","article-title":"Adaptive chromatin remodeling drives glioblastoma stem cell plasticity and drug tolerance","volume":"20","author":"Liau","year":"2017","journal-title":"Cell Stem Cell"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v10.i17.5595","article-title":"Intrathecal methotrexate in combination with systemic chemotherapy in glioblastoma patients with leptomeningeal dissemination: a retrospective analysis","volume":"10","author":"Kang","year":"2022","journal-title":"World J Clin cases"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.1001829","article-title":"Phase I\/II trial of local interstitial chemotherapy with arsenic trioxide in patients with newly diagnosed glioma","volume":"13","author":"Han","year":"2022","journal-title":"Front Neurol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1093\/neuonc\/noad143","article-title":"CDK7 and CDK9 inhibition interferes with transcription, translation, and stemness, and induces cytotoxicity in GBM irrespective of temozolomide sensitivity","volume":"26","author":"Bhutada","year":"2024","journal-title":"Neuro Oncol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1038\/nature03128","article-title":"Identification of human brain tumour initiating cells","volume":"432","author":"Singh","year":"2004","journal-title":"Nature"},{"key":"B38","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1186\/s13287-021-02231-x","article-title":"Role of glioblastoma stem cells in cancer therapeutic resistance: a perspective on antineoplastic agents from natural sources and chemical derivatives","volume":"12","author":"Alves","year":"2021","journal-title":"Stem Cell Res Ther"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.2741\/e280","article-title":"CD133 negative cancer stem cells in glioblastoma","volume":"3","author":"Beier","year":"2011","journal-title":"Front Biosci (Elite Ed)"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-4180","article-title":"CD133(+) and CD133(-) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles","volume":"67","author":"Beier","year":"2007","journal-title":"Cancer Res"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2016.230","article-title":"Differential propagation of stroma and cancer stem cells dictates tumorigenesis and multipotency","volume":"36","author":"Behnan","year":"2017","journal-title":"Oncogene"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.5114\/fn.2012.32365","article-title":"CD133\/CD15 defines distinct cell subpopulations with differential in vitro clonogenic activity and stem cell-related gene expression profile in in vitro propagated glioblastoma multiforme-derived cell line with a PNET-like component","volume":"50","author":"Kahlert","year":"2012","journal-title":"Folia Neuropathol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23094670","article-title":"A2B5 expression in central nervous system and gliomas","volume":"23","author":"Figarella-Branger","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B44","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1016\/j.cell.2019.06.024","article-title":"An integrative model of cellular states, plasticity, and genetics for glioblastoma","volume":"178","author":"Neftel","year":"2019","journal-title":"Cell"},{"key":"B45","doi-asserted-by":"publisher","first-page":"101621","DOI":"10.1016\/j.cels.2026.101621","article-title":"Widespread transcriptional memory shapes heritable states and functional heterogeneity in cancer and stem cells","author":"Lin","year":"2026","journal-title":"Cell Syst"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.130510","article-title":"Asymmetric cell division promotes therapeutic resistance in glioblastoma stem cells","volume":"6","author":"Hitomi","year":"2021","journal-title":"JCI Insight"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1093\/noajnl\/vdag002","article-title":"Epigenetic maintenance of the injury response state in glioblastoma stem cells","volume":"8","author":"Molaei","year":"2026","journal-title":"Neuro-Oncol Adv"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0315038","article-title":"CXCL12 impact on glioblastoma cells behaviors under dynamic culture conditions: insights for developing new therapeutic approaches","volume":"19","author":"El Kheir","year":"2024","journal-title":"PloS One"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2011.00495.x","article-title":"Myeloid-derived suppressor cells limit the inflammation by promoting T lymphocyte apoptosis in the spinal cord of a murine model of multiple sclerosis","volume":"21","author":"Molin\u00e9-Vel\u00e1zquez","year":"2011","journal-title":"Brain Pathol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1186\/s12974-024-03298-y","article-title":"Sentinels of neuroinflammation: the crucial role of myeloid cells in the pathogenesis of gliomas and neurodegenerative diseases","volume":"21","author":"C\u00f3mitre-Mariano","year":"2024","journal-title":"J Neuroinflamm"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-021-02872-0","article-title":"Regulatory t cells promote glioma cell stemness through TGF-\u03b2-NF-\u03baB-IL6-STAT3 signaling","volume":"70","author":"Liu","year":"2021","journal-title":"Cancer Immunol Immunother"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2446","article-title":"A human memory t cell subset with stem cell-like properties","volume":"17","author":"Gattinoni","year":"2011","journal-title":"Nat Med"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.09.034","article-title":"The somatic genomic landscape of glioblastoma","volume":"155","author":"Brennan","year":"2013","journal-title":"Cell"},{"key":"B54","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.ccell.2017.06.003","article-title":"Tumor evolution of glioma-intrinsic gene expression subtypes associates with immunological changes in the microenvironment","volume":"32","author":"Wang","year":"2017","journal-title":"Cancer Cell"},{"key":"B55","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/s12935-025-03752-8","article-title":"Unraveling anoikis in glioblastoma: insights from single-cell sequencing and prognostic modeling","volume":"25","author":"Tang","year":"2025","journal-title":"Cancer Cell Int"},{"key":"B56","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1007\/s11060-025-05036-7","article-title":"Targeting COL5A1 enhances anoikis thus attenuating Malignancy of glioblastoma via inhibiting the Wnt\/beta-catenin signaling pathway","volume":"174","author":"Zhou","year":"2025","journal-title":"J Neuro-Oncol"},{"key":"B57","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1186\/s12964-024-01623-9","article-title":"Targeting Wnt\/beta-catenin signaling and its interplay with TGF-beta and Notch signaling pathways for the treatment of chronic wounds","volume":"22","author":"Gumede","year":"2024","journal-title":"Cell Commun Signal"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3390\/cells15110991","article-title":"The signaling networks of TIM-3, TGF-beta, and STING in glioblastoma","volume":"15","author":"Ahmady-Nield","year":"2026","journal-title":"Cells"},{"key":"B59","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1080\/14737159.2024.2312102","article-title":"Tumor-infiltrating lymphocytes as a prognostic and predictive factor for Melanoma","volume":"24","author":"Vargas","year":"2024","journal-title":"Expert Rev Mol Diagn"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1497522","article-title":"Tumor-infiltrating lymphocytes in melanoma: from prognostic assessment to therapeutic applications","volume":"15","author":"Bida","year":"2024","journal-title":"Front Immunol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2023.2175506","article-title":"Tumor-infiltrating lymphocytes for melanoma immunotherapy","volume":"12","author":"Kepp","year":"2023","journal-title":"Oncoimmunology"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.808964","article-title":"Tumor-infiltrating lymphocytes in colorectal cancer: the fundamental indication and application on immunotherapy","volume":"12","author":"Bai","year":"2022","journal-title":"Front Immunol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2024.217281","article-title":"Therapeutic potential of tumor-infiltrating lymphocytes in non-small cell lung cancer","volume":"605","author":"Plaugher","year":"2024","journal-title":"Cancer Lett"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-025-04989-z","article-title":"Tumor-infiltrating and circulating B cells mediate local and systemic immunomodulatory mechanisms in glioblastoma","volume":"172","author":"De Domenico","year":"2025","journal-title":"J Neuro-Oncol"},{"key":"B65","doi-asserted-by":"publisher","first-page":"133","DOI":"10.3892\/ol.2022.13253","article-title":"Cell-based immunotherapy of glioblastoma multiforme","volume":"23","author":"Bryukhovetskiy","year":"2022","journal-title":"Oncol Lett"},{"key":"B66","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.ccr.2009.12.020","article-title":"Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1","volume":"17","author":"Verhaak","year":"2010","journal-title":"Cancer Cell"},{"key":"B67","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1126\/science.aaa6204","article-title":"T cell exclusion, immune privilege, and the tumor microenvironment","volume":"348","author":"Joyce","year":"2015","journal-title":"Science"},{"key":"B68","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.immuni.2013.07.012","article-title":"Oncology meets immunology: the cancer-immunity cycle","volume":"39","author":"Chen","year":"2013","journal-title":"Immunity"},{"key":"B69","doi-asserted-by":"publisher","first-page":"2184","DOI":"10.1016\/j.cell.2022.04.038","article-title":"Glioma progression is shaped by genetic evolution and microenvironment interactions","volume":"185","author":"Varn","year":"2022","journal-title":"Cell"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100587","article-title":"HIF-1alpha regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment","volume":"207","author":"Corzo","year":"2010","journal-title":"J Exp Med"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25021067","article-title":"The TGF-\u03b2 family in glioblastoma","volume":"25","author":"Gol\u00e1n-Cancela","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2016.5852","article-title":"Hematopoietic stem cells as a tool for the treatment of glioblastoma multiforme","volume":"14","author":"Bruykhovetskiy","year":"2016","journal-title":"Mol Med Rep"},{"key":"B73","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/s41571-020-0403-1","article-title":"TGFbeta biology in cancer progression and immunotherapy","volume":"18","author":"Derynck","year":"2021","journal-title":"Nat Rev Clin Oncol"},{"key":"B74","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/s41568-021-00413-6","article-title":"Overcoming TGFbeta-mediated immune evasion in cancer","volume":"22","author":"Tauriello","year":"2022","journal-title":"Nat Rev Cancer"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13153686","article-title":"Recent advances in glioma therapy: combining vascular normalization and immune checkpoint blockade","volume":"13","author":"Ho","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-019-0175-7","article-title":"Regulatory t cells in cancer immunosuppression - implications for anticancer therapy","volume":"16","author":"Togashi","year":"2019","journal-title":"Nat Rev Clin Oncol"},{"key":"B77","doi-asserted-by":"publisher","first-page":"898","DOI":"10.1158\/2326-6066.CIR-17-0075","article-title":"Antigen-presenting intratumoral B cells affect CD4+ TIL phenotypes in non-small cell lung cancer patients","volume":"5","author":"Bruno","year":"2017","journal-title":"Cancer Immunol Res"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2025.2538687","article-title":"Association of PD-1, LAG-3 and TIM-3 expression on intratumoral CD8 t-cells with response to atezolizumab in a real-world-evidence biomarker study for advanced urothelial carcinoma patients","volume":"14","author":"de Andrea","year":"2025","journal-title":"Oncoimmunology"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2026.1755073","article-title":"The dynamic myeloid-enriched microenvironment of glioblastoma: a major challenge to immunotherapy efficacy","volume":"17","author":"Lamorlette","year":"2026","journal-title":"Front Immunol"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1007\/s11912-023-01417-1","article-title":"Antiangiogenic therapy for Malignant brain tumors: does it still matter","volume":"25","author":"Pellerino","year":"2023","journal-title":"Curr Oncol Rep"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nor134","article-title":"Thymus-derived rather than tumor-induced regulatory t cells predominate in brain tumors","volume":"13","author":"Wainwright","year":"2011","journal-title":"Neuro Oncol"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0312-6","article-title":"Subsets of exhausted CD8+ t cells differentially mediate tumor control and respond to checkpoint blockade","volume":"20","author":"Miller","year":"2019","journal-title":"Nat Immunol"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1038\/nature19330","article-title":"Defining CD8+ t cells that provide the proliferative burst after PD-1 therapy","volume":"537","author":"Im","year":"2016","journal-title":"Nature"},{"key":"B84","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1016\/j.immuni.2020.04.014","article-title":"Developmental relationships of four exhausted CD8+ t cell subsets reveals underlying transcriptional and epigenetic landscape control mechanisms","volume":"52","author":"Beltra","year":"2020","journal-title":"Immunity"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-009449","article-title":"Inhibitory Fc\u03b3 receptor deletion enhances CD8 t cell stemness increasing anti-PD-1 therapy responsiveness against glioblastoma","volume":"12","author":"Ku","year":"2024","journal-title":"J Immunother Cancer"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14071627","article-title":"Advances in immunotherapy for the treatment of adult glioblastoma: overcoming chemical and physical barriers","volume":"14","author":"Lechpammer","year":"2022","journal-title":"Cancers (Basel)"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-25-1490","article-title":"Increased peripheral t stem cell-like memory features in patients with advanced solid tumors treated with tumor-targeting IL-12 immunocytokine therapy","volume":"31","author":"Goswami","year":"2025","journal-title":"Clin Cancer Res"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2016.1252894","article-title":"Tumor-infiltrating lymphocytes (TILs) from patients with glioma","volume":"6","author":"Liu","year":"2016","journal-title":"Oncoimmunology"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-00565-9","article-title":"Tumor-infiltrating lymphocytes in the immunotherapy era","volume":"18","author":"Paijens","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14061558","article-title":"Tumor-infiltrating lymphocytes in head and neck cancer: ready for prime time","volume":"14","author":"Almangush","year":"2022","journal-title":"Cancers (Basel)"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1093\/stcltm\/szaf020","article-title":"Anti-viral CD8 central memory veto cells as a new platform for CAR t cell therapy","volume":"14","author":"Liu","year":"2025","journal-title":"Stem Cells Transl Med"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-021-00973-w","article-title":"Effector memory cytotoxic CD3(+)\/CD8(+)\/CD45RO(+) t cells are predictive of good survival and a lower risk of recurrence in triple-negative breast cancer","volume":"35","author":"Sun","year":"2022","journal-title":"Mod Pathol"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2022030286","article-title":"Effector memory-expressing CD45RA (TEMRA) CD8(+) t cells from kidney transplant recipients exhibit enhanced purinergic P2X4 receptor-dependent proinflammatory and migratory responses","volume":"33","author":"Doan Ngoc","year":"2022","journal-title":"J Am Soc Nephrol"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.834889","article-title":"The role of DNA repair in immunological diversity: from molecular mechanisms to clinical ramifications","volume":"13","author":"Gulliksson","year":"2022","journal-title":"Front Immunol"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20241433","article-title":"Epigenetic priming as a driver of memory recall and dysfunction in t cells","volume":"222","author":"Metzemaekers","year":"2025","journal-title":"J Exp Med"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.3390\/biom13010084","article-title":"DNA repair and immune response: editorial","volume":"13","author":"Oksenych","year":"2022","journal-title":"Biomolecules"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1034689","article-title":"Editorial: DNA repair and immune response","volume":"13","author":"Basso","year":"2022","journal-title":"Front Immunol"},{"key":"B98","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1038\/s41467-024-55455-9","article-title":"Oncolytic reprogramming of tumor microenvironment shapes CD4 t-cell memory via the IL6ra-Bcl6 axis for targeted control of glioblastoma","volume":"16","author":"Grimes","year":"2025","journal-title":"Nat Commun"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-005293","article-title":"Impact of CD4 t cells on intratumoral CD8 t-cell exhaustion and responsiveness to PD-1 blockade therapy in mouse brain tumors","volume":"10","author":"Khan","year":"2022","journal-title":"J Immunother Cancer"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24044253","article-title":"Dendritic cell and cancer therapy","volume":"24","author":"Galati","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.23.021704.115825","article-title":"Cooperation between CD4+ and CD8+ T cells: when, where, and how","volume":"24","author":"Castellino","year":"2006","journal-title":"Annu Rev Immunol"},{"key":"B102","doi-asserted-by":"publisher","first-page":"1612","DOI":"10.1016\/j.cell.2020.05.017","article-title":"Intratumoral CD4+ T cells mediate anti-tumor cytotoxicity in human bladder cancer","volume":"181","author":"Oh","year":"2020","journal-title":"Cell"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202310282","article-title":"Spatiotemporal analysis of mesenchymal stem cells fate determination by inflammatory niche following soft tissue injury at a single-cell level","volume":"11","author":"Kan","year":"2024","journal-title":"Adv Sci (Weinh)"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-019-0144-6","article-title":"Tertiary lymphoid structures in the era of cancer immunotherapy","volume":"19","author":"Saut\u00e8s-Fridman","year":"2019","journal-title":"Nat Rev Cancer"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1172\/JCI67428","article-title":"CD4+ follicular helper T cell infiltration predicts breast cancer survival","volume":"123","author":"Gu-Trantien","year":"2013","journal-title":"J Clin Invest"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.14670\/HH-18-366","article-title":"TGF-beta links glycolysis and immunosuppression in glioblastoma","volume":"36","author":"Gong","year":"2021","journal-title":"Histol Histopathol"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1093\/noajnl\/vdaf242","article-title":"Phase 1 LITESPARK-001 study of belzutifan in participants with advanced solid tumors: results of the glioblastoma expansion cohort","volume":"8","author":"Strowd","year":"2025","journal-title":"Neuro-Oncol Adv"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2024.02.007","article-title":"Nanoparticle-mediated blockade of CXCL12\/CXCR4 signaling enhances glioblastoma immunotherapy: monitoring early responses with MRI radiomics","volume":"177","author":"Wei","year":"2024","journal-title":"Acta Biomater"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2024.153898","article-title":"Bisphenol S (BPS) induces glioblastoma progression via regulation of EZH2-mediated PI3K\/AKT\/mTOR pathway in U87-MG cells","volume":"507","author":"Ko","year":"2024","journal-title":"Toxicology"},{"key":"B110","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1158\/2326-6066.CIR-24-0089","article-title":"Transient EZH2 suppression by tazemetostat during in vitro expansion maintains T-cell stemness and improves adoptive T-cell therapy","volume":"13","author":"Hou","year":"2025","journal-title":"Cancer Immunol Res"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noac107","article-title":"Decitabine increases neoantigen and cancer testis antigen expression to enhance T-cell-mediated toxicity against glioblastoma","volume":"24","author":"Ma","year":"2022","journal-title":"Neuro Oncol"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.2174\/0118715273330268241008220702","article-title":"Valproic acid and celecoxib enhance the effect of temozolomide on glioblastoma cells","volume":"24","author":"Pak","year":"2025","journal-title":"CNS Neurol Disord Drug Targets"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2022.5370","article-title":"Association of autologous tumor lysate-loaded dendritic cell vaccination with extension of survival among patients with newly diagnosed and recurrent glioblastoma: a phase 3 prospective externally controlled cohort trial","volume":"9","author":"Liau","year":"2023","journal-title":"JAMA Oncol"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-0261","article-title":"A randomized double-blind placebo-controlled phase II trial of dendritic cell vaccine ICT-107 in newly diagnosed patients with glioblastoma","volume":"25","author":"Wen","year":"2019","journal-title":"Clin Cancer Res"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.21037\/tcr-2020-004","article-title":"Vaccines against glioblastoma: reflections on the ICT-107 phase IIb trial","volume":"9","author":"De Vleeschouwer","year":"2020","journal-title":"Transl Cancer Res"},{"key":"B116","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s13045-025-01661-x","article-title":"WT1-mRNA dendritic cell vaccination of patients with glioblastoma multiforme, Malignant pleural mesothelioma, metastatic breast cancer, and other solid tumors: type 1 T-lymphocyte responses are associated with clinical outcome","volume":"18","author":"Berneman","year":"2025","journal-title":"J Hematol Oncol"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1093\/noajnl\/vdaf051","article-title":"Translational advancements in tumor vaccine therapies for glioblastomas","volume":"7","author":"Jha","year":"2025","journal-title":"Neuro-Oncol Adv"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0810-y","article-title":"Actively personalized vaccination trial for newly diagnosed glioblastoma","volume":"565","author":"Hilf","year":"2019","journal-title":"Nature"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2021.100214","article-title":"Emerging targets for anticancer vaccination: IDH","volume":"6","author":"Platten","year":"2021","journal-title":"ESMO Open"},{"key":"B120","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1007\/s00262-025-04178-x","article-title":"Preclinical development of an mRNA-based multiepitope immunotherapeutic for glioblastoma","volume":"74","author":"Lutz","year":"2025","journal-title":"Cancer Immunol Immunother"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.773264","article-title":"Identification of tumor antigens and immune subtypes of glioblastoma for mRNA vaccine development","volume":"13","author":"Lin","year":"2022","journal-title":"Front Immunol"},{"key":"B122","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/s40537-022-00643-x","article-title":"Tumor antigens and immune subtypes of glioblastoma: the fundamentals of mRNA vaccine and individualized immunotherapy development","volume":"9","author":"Wu","year":"2022","journal-title":"J Big Data"},{"key":"B123","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s41016-022-00301-4","article-title":"Identification of tumor-associated antigens and immune subtypes of lower-grade glioma and glioblastoma for mRNA vaccine development","volume":"8","author":"Wang","year":"2022","journal-title":"Chin Neurosurg J"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-023-09376-2","article-title":"Targeting tumor microenvironment using tumor-infiltrating lymphocytes as therapeutics against tumorigenesis","volume":"71","author":"Qayoom","year":"2023","journal-title":"Immunol Res"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2017.1.693","article-title":"Graft versus tumor effects and why people relapse","volume":"2017","author":"Falkenburg","year":"2017","journal-title":"Hematol Am Soc Hematol Educ Program"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.00203","article-title":"Irinotecan, temozolomide, and dinutuximab with GM-CSF in children with refractory or relapsed neuroblastoma: a report from the Children's Oncology Group","volume":"38","author":"Mody","year":"2020","journal-title":"J Clin Oncol"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1186\/2051-1426-2-S3-P27","article-title":"Rapid expansion of TILs from patients with glioma and recognition of autologous tumor","volume":"2","author":"Zhenjiang","year":"2014","journal-title":"J Immunother Cancer"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1018962","article-title":"Tumor-infiltrating lymphocytes for treatment of solid tumors: it takes two to tango","volume":"13","author":"Kazemi","year":"2022","journal-title":"Front Immunol"},{"key":"B129","doi-asserted-by":"publisher","first-page":"7279","DOI":"10.1038\/s41467-025-62263-2","article-title":"Polyclonal expansion of functional tumor-reactive lymphocytes infiltrating glioblastoma for personalized cell therapy","volume":"16","author":"Maffezzini","year":"2025","journal-title":"Nat Commun"},{"key":"B130","unstructured":"Methods of producing T memory stem cell populations\n          \n          \n            \n              Gattinoni\n              L\n            \n            \n              Lugli\n              E\n            \n            \n              Roederer\n              M\n            \n            \n              Restifo\n              NP\n            \n          \n          \n          2021"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.973881","article-title":"Why do tumor-infiltrating lymphocytes have variable efficacy in the treatment of solid tumors","volume":"13","author":"Li","year":"2022","journal-title":"Front Immunol"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.26717\/BJSTR.2022.47.007462","article-title":"Machine-learning modeling for personalized immunotherapy- an evaluation module","volume":"47","author":"Ying","year":"2022","journal-title":"BioMed J Sci Tech Res"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2024.11.013","article-title":"The clinical TIL experience in melanoma: past, present, future","volume":"31","author":"Smithy","year":"2025","journal-title":"Transplant Cell Ther"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.33549\/physiolres.935155","article-title":"Tumor-infiltrating lymphocytes and adoptive cell therapy: state of the art in colorectal, breast and lung cancer","volume":"72","author":"Zemanek","year":"2023","journal-title":"Physiol Res"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20050732","article-title":"Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells","volume":"202","author":"Gattinoni","year":"2005","journal-title":"J Exp Med"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20142290","article-title":"A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules","volume":"212","author":"Aspelund","year":"2015","journal-title":"J Exp Med"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.1089\/cbr.2005.20.11","article-title":"Administration of high-dose continuous infusion interleukin-2 to patients age 70 or over","volume":"20","author":"Quan Jr","year":"2005","journal-title":"Cancer Biother Radiopharm"},{"key":"B138","doi-asserted-by":"crossref","DOI":"10.1097\/00002371-200307000-00005","article-title":"Generation of tumor-infiltrating lymphocyte cultures for use in adoptive transfer therapy for melanoma patients","volume":"26","author":"Dudley","year":"2003","journal-title":"J Immunother"},{"key":"B139","doi-asserted-by":"crossref","DOI":"10.1126\/science.1076514","article-title":"Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes","volume":"298","author":"Dudley","year":"2002","journal-title":"Science"},{"key":"B140","doi-asserted-by":"crossref","DOI":"10.1200\/JCO.2006.09.9861","article-title":"Chemotherapy delivery issues in central nervous system malignancy: a reality check","volume":"25","author":"Muldoon","year":"2007","journal-title":"J Clin Oncol"},{"key":"B141","doi-asserted-by":"crossref","DOI":"10.1056\/NEJMoa1012863","article-title":"gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma","volume":"364","author":"Schwartzentruber","year":"2011","journal-title":"N Engl J Med"},{"key":"B142","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcskn.2026.100881","article-title":"A-539 - PragmaTIL: A randomized phase II study evaluating an IL-2 analogue (ANV419) versus high-dose IL-2 following tumor-infiltrating lymphocyte (TIL) therapy in advanced melanoma","volume":"4","author":"Lostes Bardaji","year":"2026","journal-title":"EJC Skin Cancer"},{"key":"B143","doi-asserted-by":"publisher","DOI":"10.1186\/s12865-024-00676-2","article-title":"Long-term survival after local immunotherapy for malignant gliomas: a retrospective study with 20 years follow-up","volume":"25","author":"Duan","year":"2024","journal-title":"BMC Immunol"},{"key":"B144","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-018-0391-1","article-title":"Adoptive transfer of tumor-infiltrating lymphocytes in melanoma: a viable treatment option","volume":"6","author":"Rohaan","year":"2018","journal-title":"J Immunother Cancer"},{"key":"B145","doi-asserted-by":"publisher","DOI":"10.1101\/2025.03.26.645566","article-title":"A Spatial Multi-Omic Framework Identifies Gliomas Permissive to TIL Expansion","author":"Hotchkiss","year":"2025","journal-title":"bioRxiv"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1880908\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:53:40Z","timestamp":1784699620000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1880908\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,22]]},"references-count":145,"alternative-id":["10.3389\/fimmu.2026.1880908"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1880908","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,22]]},"article-number":"1880908"}}