ArticleHaematologica2021
Combining ibrutinib and checkpoint blockade improves CD8+ T-cell function and control of chronic lymphocytic leukemia in Em-TCL1 mice.
Article in Haematologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 40 citations in OpenAlex.
- Phase 2 trial of ibrutinib and nivolumab in patients with relapsed CNS lymphomas.Blood advances · 2025Trial
- Bruton's Tyrosine Kinase Inhibitors: Mechanisms, Efficacy, Toxicities and Applications for the Treatment of Human Diseases.MedComm · 2026Review
- Mechanisms of resistance to bruton's tyrosine kinase inhibitors: synergistic effects of tumor microenvironment regulation and signaling pathways.Annals of hematology · 2026Review
- Non-Malignant T Cells as Determinants of Immunotherapeutic Response in Chronic Lymphocytic Leukemia: Towards Personalized Strategies.Oncology research · 2026Review
- Enhancing immunotherapy efficacy in multiple myeloma and chronic lymphocytic leukemia: from combinatorial therapeutic approaches to gut microbiota modulation.Frontiers in immunology · 2026Review
- Review
- Effects of ibrutinib and venetoclax on the expression of immune checkpoint molecules in leukemic blasts of patients with acute lymphoblastic leukemia.Biochemistry and biophysics reports · 2025Article
- Targeting interleukin-2-inducible T cell kinase ameliorates immune-mediated aplastic anemia.Cancer immunology, immunotherapy : CII · 2025Article
- Targeting PD-L1 for PCNS-DLBCL: from molecular effects to clinical translation.Frontiers in immunology · 2025Review
- Review
- Promising Therapeutic Strategies for Hematologic Malignancies: Innovations and Potential.Molecules (Basel, Switzerland) · 2024Review
- Current Approaches of Immune Checkpoint Therapy in Chronic Lymphocytic Leukemia.Current treatment options in oncology · 2023Review
- Sulfamate Acetamides as Self-Immolative Electrophiles for Covalent Ligand-Directed Release Chemistry.Journal of the American Chemical Society · 2023Article
- BTK inhibitor combined with anti-PD-1 monoclonal antibody for the treatment of CD20-negative primary central nervous system lymphoma: A case report.Oncology letters · 2023Article
- Ibrutinib directly reduces CD8+T cell exhaustion independent of BTK.Frontiers in immunology · 2023Article
- Regulatory effects of IRF4 on immune cells in the tumor microenvironment.Frontiers in immunology · 2023Review
- Viral transduction of primary human lymphoma B cells reveals mechanisms of NOTCH-mediated immune escape.Nature communications · 2022Article
- Article
- Combined Blockade Of PD-1 and TIGIT is not Sufficient to Improve the Function Of CD8+ T-Cells in Chronic Lymphocytic Leukemia.Asian Pacific journal of cancer prevention : APJCP · 2022Article
- Effects of ibrutinib on T-cell immunity in patients with chronic lymphocytic leukemia.Frontiers in immunology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ibrutinib is a bruton's tyrosine kinase (BTK) inhibitor approved for the treatment of multiple B-cell malignancies, including chronic lymphocytic leukemia (CLL). In addition to blocking B-cell receptor signaling and chemokine receptor-mediated pathways in CLL cells, that are known drivers of disease, ibrutinib also affects the microenvironment in CLL via targeting BTK in myeloid cells and IL-2-inducible T-cell kinase (ITK) in T-cells. These non-BTK effects were suggested to contribute to the success of ibrutinib in CLL. By using the Eµ-TCL1 adoptive transfer mouse model of CLL, we observed that ibrutinib effectively controls leukemia development, but also results in significantly lower numbers of CD8+ effector T-cells, with lower expression of activation markers, as well as impaired proliferation and effector function. Using CD8+ T-cells from a T-cell receptor (TCR) reporter mouse, we verified that this is due to a direct effect of ibrutinib on TCR activity, and demonstrate that co-stimulation via CD28 overcomes these effects. Most interestingly, combination of ibrutinib with blocking antibodies targeting PD-1/PD-L1 axis in vivo improved CD8+ T-cell effector function and control of CLL. In sum, these data emphasize the strong immunomodulatory effects of ibrutinib and the therapeutic potential of its combination with immune checkpoint blockade in CLL.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.