ArticleClinical cancer research : an official journal of the American Association for Cancer Research2020
4-1BB Agonism Averts TIL Exhaustion and Licenses PD-1 Blockade in Glioblastoma and Other Intracranial Cancers.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 65 citations in OpenAlex.
- Review
- CD8MedComm · 2026Review
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Immune remodeling of tumor-draining lymph nodes: mechanistic determinants of checkpoint blockade responsiveness.Frontiers in immunology · 2026Review
- Multiple autologous tumor-infiltrating lymphocyte (LM103 infusion) therapy combined with immune checkpoint inhibitor induces repeated tumor regression in a patient with aggressive mucosal melanoma: a case report and literature review.Frontiers in oncology · 2026Article
- Role of elevation of glycolysis in tumor-associated macrophages in glioblastoma immune evasion and therapeutic implications.PNAS nexus · 2026Review
- Multiomics Investigation of Exhausted T Cells in Glioblastoma Tumor Microenvironment:International journal of molecular sciences · 2025Article
- Functional Reprogramming of Neutrophils within the Brain Tumor Microenvironment by Hypoxia-Driven Histone Lactylation.Cancer discovery · 2025Article
- IL-7-mediated expansion of autologous lymphocytes increases CD8bioRxiv : the preprint server for biology · 2025Article
- Acasunlimab, an Fc-inert PD-L1×4-1BB bispecific antibody, combined with PD-1 blockade potentiates antitumor immunity via complementary immune modulatory effects.Journal for immunotherapy of cancer · 2025Article
- Bispecific antibody for lung cancer: mechanisms and clinical insights.Frontiers in immunology · 2025Review
- Combining immune checkpoints with TNFSF agonists: a new horizon for cancer and autoimmune therapies.Frontiers in immunology · 2025Article
- Targeting tumor-draining lymph node to overcome resistance to cancer immunotherapy: an update.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Cell Identity and Spatial Distribution of PD-1/PD-L1 Blockade Responders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- SAIL66, a next generation CLDN6-targeting T-cell engager, demonstrates potent antitumor efficacy through dual binding to CD3/CD137.Journal for immunotherapy of cancer · 2024Article
- Armored bicistronic CAR T cells with dominant-negative TGF-β receptor II to overcome resistance in glioblastoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- ATG-101 Is a Tetravalent PD-L1×4-1BB Bispecific Antibody That Stimulates Antitumor Immunity through PD-L1 Blockade and PD-L1-Directed 4-1BB Activation.Cancer research · 2024Article
- From glioma gloom to immune bloom: unveiling novel immunotherapeutic paradigms-a review.Journal of experimental & clinical cancer research : CR · 2024Review
- Increased co-expression of 4-1BB with PD-1 on CD8+ tumor-infiltrating lymphocytes is associated with improved prognosis and immunotherapy response in cervical cancer.Frontiers in oncology · 2024Article
- CXCL10 and Nrf2-upregulated mesenchymal stem cells reinvigorate T lymphocytes for combating glioblastoma.Journal for immunotherapy of cancer · 2023Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
purposeThe success of checkpoint blockade against glioblastoma (GBM) has been disappointing. Anti-PD-1 strategies may be hampered by severe T-cell exhaustion. We sought to develop a strategy that might license new efficacy for checkpoint blockade in GBM. EXPERIMENTAL
designWe characterized 4-1BB expression in tumor-infiltrating lymphocytes (TIL) from human GBM. We implanted murine tumor models including glioma (CT2A), melanoma (B16), breast (E0771), and lung carcinomas intracranially and subcutaneously, characterized 4-1BB expression, and tested checkpoint blockade strategies
resultsOur data reveal that 4-1BB is frequently present on nonexhausted CD8
conclusionsAlthough poor T-cell activation and severe T-cell exhaustion appear to be limiting factors for checkpoint blockade in GBM, 4-1BB agonism obviates these limitations and produces long-term survival when combined with anti-PD-1 therapy. Furthermore, this combination therapy is limited by TIL 4-1BB expression, but not by the intracranial compartment, and therefore may be particularly well-suited to GBM.
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