ArticleEuropean journal of immunology2021
4-1BB costimulation promotes bystander activation of human CD8 T cells.
Article in European journal of immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Selective elimination of circulating effector CD8 T cells via LTβR blockade separates anti-CD137 efficacy from toxicity.Science advances · 2026Article
- Mechanisms of T cell activation: Integrating signaling pathways, experimental models, and therapeutic implications.EXCLI journal · 2026Review
- Human CD4+ T cells recognize Mycobacterium tuberculosis-infected macrophages amid broader responses.The Journal of experimental medicine · 2025Article
- Intratumoral delivery of 4-1BBL boosts IL-12-triggered anti-glioma immunity.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Transitioning from native to synthetic receptors: broadening T-cell engineering and beyond.Cellular & molecular immunology · 2025Review
- Decoding MHC loss: Molecular mechanisms and implications for immune resistance in cancer.Clinical and translational medicine · 2025Review
- TIGIT contributes to the regulation of 4-1BB and does not define NK cell dysfunction in glioblastoma.iScience · 2023Article
- Engineered soluble, trimerized 4-1BBL variants as potent immunomodulatory agents.Cancer immunology, immunotherapy : CII · 2023Article
- Polymeric nanoparticle gel for intracellular mRNA delivery and immunological reprogramming of tumors.Biomaterials · 2023Article
- Expansion of KRAS hotspot mutations reactive T cells from human pancreatic tumors using autologous T cells as the antigen-presenting cells.Cancer immunology, immunotherapy : CII · 2023Article
- PLEK2 and IFI6, representing mesenchymal and immune-suppressive microenvironment, predicts resistance to neoadjuvant immunotherapy in esophageal squamous cell carcinoma.Cancer immunology, immunotherapy : CII · 2023Article
- FcγR requirements and costimulatory capacity of Urelumab, Utomilumab, and Varlilumab.Frontiers in immunology · 2023Article
- Killer instincts: natural killer cells as multifactorial cancer immunotherapy.Frontiers in immunology · 2023Review
- Serum Concentration of CD137 and Tumor Infiltration by M1 Macrophages Predict the Response to Sintilimab plus Bevacizumab Biosimilar in Advanced Hepatocellular Carcinoma Patients.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Preclinical Characterization and Phase I Trial Results of a Bispecific Antibody Targeting PD-L1 and 4-1BB (GEN1046) in Patients with Advanced Refractory Solid Tumors.Cancer discovery · 2022Article
- Advanced development of biomarkers for immunotherapy in hepatocellular carcinoma.Frontiers in oncology · 2022Review
- Engaging the Innate and Adaptive Antitumor Immune Response in Lymphoma.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Costimulatory signals potently promote T-cell proliferation and effector function. Agonistic antibodies targeting costimulatory receptors of the TNFR family, such as 4-1BB and CD27, have entered clinical trials in cancer patients. Currently there is limited information how costimulatory signals regulate antigen-specific but also bystander activation of human CD8 T cells. Engineered antigen presenting cells (eAPC) efficiently presenting several common viral epitopes on HLA-A2 in combination with MHC class I tetramer staining were used to investigate the impact of costimulatory signals on human CD8 T-cell responses. CD28 costimulation potently augmented the percentage and number of antigen-reactive CD8 T cells, whereas eAPC expressing 4-1BB-ligand induced bystander proliferation of CD8 T cells and massive expansion of NK cells. Moreover, the 4-1BB agonist urelumab similarly induced bystander proliferation of CD8 T cells and NK cells in a dose-dependent manner. However, the promotion of bystander CD8 T-cell responses is not a general attribute of costimulatory TNF receptor superfamily (TNFRSF) members, since CD27 signals enhanced antigen-specific CD8 T cells responses without promoting significant bystander activation. Thus, the differential effects of costimulatory signals on the activation of human bystander CD8 T cells should be taken into account when costimulatory pathways are harnessed for cancer immunotherapy.
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