Endogenous immune recruitment in glioblastoma CAR T therapy: cytokine, myeloid, and chemokine circuitry

Price M, Ballard C, Benedetti J et al (2024) CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2017–2021. Neuro-Oncol 26:vi1–vi85

Article  PubMed  PubMed Central  Google Scholar 

Durga YK, Pusapati RV (2026) Drug resistance in glioblastoma: Challenges, mechanisms and therapeutic strategies (Review). Mol Clin Oncol 24:4

PubMed  Google Scholar 

Wang X, Guo G, Guan H et al (2019) Challenges and potential of PD-1/PD-L1 checkpoint blockade immunotherapy for glioblastoma. J Exp Clin Cancer Res CR 38:87

CAS  PubMed  PubMed Central  Google Scholar 

Abikenari MA, Enayati I, Fountain DM et al (2024) Navigating glioblastoma therapy: A narrative review of emerging immunotherapeutics and small-molecule inhibitors. Microbes Immun 0:5075

Google Scholar 

Dynarowicz K, Smolak B, Bartusik-Aebisher D et al (2026) Current Pharmacotherapeutic Strategies in Diffuse Gliomas: Focus on Glioblastoma, IDH-Wildtype, and Emerging Targeted Therapies for IDH-Mutant Tumors. Pharmaceuticals 19:148

Article  PubMed  PubMed Central  Google Scholar 

Abikenari M, Schonfeld E, Choi J et al (2024) Revisiting glioblastoma classification through an immunological lens: A narrative review. Glioma 7:3–9

Article  Google Scholar 

Wu L, Wei Q, Brzostek J et al (2020) Signaling from T cell receptors (TCRs) and chimeric antigen receptors (CARs) on T cells. Cell Mol Immunol 17:600–612

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ershova A, Goldaeva A, Staliarova A et al Future perspectives on novel CAR-T therapeutics beyond CD19 and BCMA in onco-hematology. Front Immunol. 16. Epub ahead of print 14 July 2025. https://doi.org/10.3389/fimmu.2025.1592377.

Awasthi R, Maier HJ, Zhang J et al (2023) Kymriah® (tisagenlecleucel) - An overview of the clinical development journey of the first approved CAR-T therapy. Hum Vaccines Immunother 19:2210046

Article  Google Scholar 

Ahmad A, Uddin S, Steinhoff M, CAR-T Cell Therapies (2020) An Overview of Clinical Studies Supporting Their Approved Use against Acute Lymphoblastic Leukemia and Large B-Cell Lymphomas. Int J Mol Sci 21:3906

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gene targets of CAR-T cell therapy for glioblastoma - PMC https://pmc.ncbi.nlm.nih.gov/articles/PMC10136592/. Accessed 21 Jan 2026.

MacKay M, Afshinnekoo E, Rub J et al (2020) The therapeutic landscape for cells engineered with chimeric antigen receptors. Nat Biotechnol 38:233–244

Article  CAS  PubMed  Google Scholar 

Krenciute G, Prinzing BL, Yi Z et al (2017) Transgenic Expression of IL15 Improves Antiglioma Activity of IL13Rα2-CAR T Cells but Results in Antigen Loss Variants. Cancer Immunol Res 5:571–581

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sampson JH, Heimberger AB, Archer GE et al (2010) Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma. J Clin Oncol Off J Am Soc Clin Oncol 28:4722–4729

Article  Google Scholar 

O’Rourke DM, Nasrallah MP, Desai A et al (2017) A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci Transl Med 9:eaaa0984

Article  PubMed  PubMed Central  Google Scholar 

Brown CE, Alizadeh D, Starr R et al (2016) Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy. N Engl J Med 375:2561–2569

Article  CAS  PubMed  PubMed Central  Google Scholar 

Medikonda R, Abikenari MA, Schonfeld E et al (2025) Top advances of the year: The status of chimeric antigen receptor T cells in neuro-oncology. Cancer 131:e35935

Article  PubMed  Google Scholar 

Skaga E, Kulesskiy E, Fayzullin A et al (2019) Intertumoral heterogeneity in patient-specific drug sensitivities in treatment-naïve glioblastoma. BMC Cancer 19:628

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sottoriva A, Spiteri I, Piccirillo SGM et al (2013) Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics. Proc Natl Acad Sci 110:4009–4014

Article  CAS  PubMed  PubMed Central  Google Scholar 

Neftel C, Laffy J, Filbin MG et al (2019) An Integrative Model of Cellular States, Plasticity, and Genetics for Glioblastoma. Cell 178:835–849e21

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gabrusiewicz K, Rodriguez B, Wei J et al (2016) Glioblastoma-infiltrated innate immune cells resemble M0 macrophage phenotype. JCI Insight 1:e85841

Article  PubMed  PubMed Central  Google Scholar 

Orrego E, Castaneda CA, Castillo M et al (2018) Distribution of tumor-infiltrating immune cells in glioblastoma. CNS Oncol 7:CNS21

Article  PubMed  PubMed Central  Google Scholar 

Maas AIR, Stocchetti N, Bullock R (2008) Moderate and severe traumatic brain injury in adults. Lancet Neurol 7:728–741

Article  PubMed  Google Scholar 

Medikonda R, Abikenari M, Schonfeld E et al (2025) The Metabolic Orchestration of Immune Evasion in Glioblastoma: From Molecular Perspectives to Therapeutic Vulnerabilities. Cancers 17:1881

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mohme M, Schliffke S, Maire CL et al (2018) Immunophenotyping of Newly Diagnosed and Recurrent Glioblastoma Defines Distinct Immune Exhaustion Profiles in Peripheral and Tumor-infiltrating Lymphocytes. Clin Cancer Res Off J Am Assoc Cancer Res 24:4187–4200

Article  CAS  Google Scholar 

Woroniecka K, Chongsathidkiet P, Rhodin K et al (2018) T-Cell Exhaustion Signatures Vary with Tumor Type and Are Severe in Glioblastoma. Clin Cancer Res Off J Am Assoc Cancer Res 24:4175–4186

Article  CAS  Google Scholar 

Hu B, Ren J, Luo Y et al (2017) Augmentation of antitumor immunity by human and mouse CAR T cells secreting IL-18. Cell Reports. 20(13):3025–3033. Accessed 21 Jan 2026.

Yeku OO, Brentjens RJ (2016) Armored CAR T-cells: utilizing cytokines and pro-inflammatory ligands to enhance CAR T-cell anti-tumour efficacy. Biochem Soc Trans 44:412–418

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen M, Sun R, Shi B et al (2019) Antitumor efficacy of chimeric antigen receptor T cells against EGFRvIII-expressing glioblastoma in C57BL/6 mice. Biomed Pharmacother 113:108734

Article  CAS  PubMed  Google Scholar 

Sampson JH, Choi BD, Sanchez-Perez L et al (2014) EGFRvIII mCAR-modified T-cell therapy cures mice with established intracerebral glioma and generates host immunity against tumor-antigen loss. Clin Cancer Res Off J Am Assoc Cancer Res 20:972–984

Article  CAS  Google Scholar 

Denlinger N, Bond D, Jaglowski S (2022) CAR T-cell therapy for B-cell lymphoma. Curr Probl Cancer 46:100826

Article  PubMed  Google Scholar 

Cappell KM, Kochenderfer JN (2023) Long-term outcomes following CAR T cell therapy: what we know so far. Nat Rev Clin Oncol 20:359–371

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wudhikarn K, Flynn JR, Rivière I et al (2021) Interventions and outcomes of adult patients with B-ALL progressing after CD19 chimeric antigen receptor T-cell therapy. Blood 138:531–543

Article  CAS  PubMed  PubMed Central  Google Scholar 

Maude SL, Frey N, Shaw PA et al (2014) Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med 371:1507–1517

Article  PubMed  PubMed Central  Google Scholar 

Park JH, Rivière I, Gonen M et al (2018) Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia. N Engl J Med 378:449–459

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