ArticleBlood2021
Triggering interferon signaling in T cells with avadomide sensitizes CLL to anti-PD-L1/PD-1 immunotherapy.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Mortality of COVID-19 in patients with hematological malignancies versus solid tumors: a systematic literature review and meta-analysis.Clinical and experimental medicine · 2023Pooled it
- Polyfunctional CD8Molecular oncology · 2025Article
- Targeted protein degradation: advances in drug discovery and clinical practice.Signal transduction and targeted therapy · 2024Review
- Article
- p66Shc deficiency in CLL cells enhances PD-L1 expression and suppresses immune synapse formation.Frontiers in cell and developmental biology · 2024Article
- Preparation of genetically or chemically engineered exosomes and their therapeutic effects in bone regeneration and anti-inflammation.Frontiers in bioengineering and biotechnology · 2024Review
- The progress of novel strategies on immune-based therapy in relapsed or refractory diffuse large B-cell lymphoma.Experimental hematology & oncology · 2023Review
- Pharmacologic targeting of Nedd8-activating enzyme reinvigorates T-cell responses in lymphoid neoplasia.Leukemia · 2023Article
- Extracellular Vesicle Secretion by Leukemia Cells In Vivo Promotes CLL Progression by Hampering Antitumor T-cell Responses.Blood cancer discovery · 2023Article
- Progress of research on PD-1/PD-L1 in leukemia.Frontiers in immunology · 2023Review
- The E3 ubiquitin ligases regulate PD-1/PD-L1 protein levels in tumor microenvironment to improve immunotherapy.Frontiers in immunology · 2023Review
- Learning from TCR Signaling and Immunological Synapse Assembly to Build New Chimeric Antigen Receptors (CARs).International journal of molecular sciences · 2022Review
- Viral transduction of primary human lymphoma B cells reveals mechanisms of NOTCH-mediated immune escape.Nature communications · 2022Article
- Exosomal PD-L1 induces osteogenic differentiation and promotes fracture healing by acting as an immunosuppressant.Bioactive materials · 2022Article
- Review
- Immunotherapeutic Strategies in Chronic Lymphocytic Leukemia: Advances and Challenges.Frontiers in oncology · 2022Review
- Targeting Cancer Cell Ferroptosis to Reverse Immune Checkpoint Inhibitor Therapy Resistance.Frontiers in cell and developmental biology · 2022Review
- Noncanonical PD-1/PD-L1 Axis in Relation to the Efficacy of Anti-PD Therapy.Frontiers in immunology · 2022Review
- GNAI2 Is a Risk Factor for Gastric Cancer: Study of Tumor Microenvironment (TME) and Establishment of Immune Risk Score (IRS).Oxidative medicine and cellular longevity · 2022Article
- Reshaping the tumor microenvironment: The versatility of immunomodulatory drugs in B-cell neoplasms.Frontiers in immunology · 2022Review
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22 authors at 10 institutions in 4 countries.
Funding
Abstract
Cancer treatment has been transformed by checkpoint blockade therapies, with the highest anti-tumor activity of anti-programmed death 1 (PD-1) antibody therapy seen in Hodgkin lymphoma. Disappointingly, response rates have been low in the non-Hodgkin lymphomas, with no activity seen in relapsed/refractory chronic lymphocytic leukemia (CLL) with PD-1 blockade. Thus, identifying more powerful combination therapy is required for these patients. Here, we preclinically demonstrate enhanced anti-CLL activity following combinational therapy with anti-PD-1 or anti-PD-1 ligand (PD-L1) and avadomide, a cereblon E3 ligase modulator (CELMoD). Avadomide induced type I and II interferon (IFN) signaling in patient T cells, triggering a feedforward cascade of reinvigorated T-cell responses. Immune modeling assays demonstrated that avadomide stimulated T-cell activation, chemokine expression, motility and lytic synapses with CLL cells, as well as IFN-inducible feedback inhibition through upregulation of PD-L1. Patient-derived xenograft tumors treated with avadomide were converted to CD8+ T cell-inflamed tumor microenvironments that responded to anti-PD-L1/PD-1-based combination therapy. Notably, clinical analyses showed increased PD-L1 expression on T cells, as well as intratumoral expression of chemokine signaling genes in B-cell malignancy patients receiving avadomide-based therapy. These data illustrate the importance of overcoming a low inflammatory T-cell state to successfully sensitize CLL to checkpoint blockade-based combination therapy.
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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.