ArticleCancer discovery2023
BCL2 Inhibition Reveals a Dendritic Cell-Specific Immune Checkpoint That Controls Tumor Immunosurveillance.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 64 citations in OpenAlex.
- Enhancing immunogenic cell death by targeting the GPX4-ZP3 immune checkpoint.Oncoimmunology · 2026Article
- The immunology of human breast cancer.Nature reviews. Immunology · 2026Review
- SEVs-carried ENPP1 regulates DCs' activation and inhibits the formation of tertiary lymphoid structures in gastric cancer.Journal of gastroenterology · 2026Article
- Personalized targeting of BCL2 family proteins overcomes acquired resistance to BRAF-MEK inhibitors in preclinical melanoma.Nature communications · 2026Article
- A cross-talk between p16High senescence and cellular reprogramming.Clinical science (London, England : 1979) · 2026Review
- Integrated proteomic and single-nucleus transcriptomic profiling identifies prognostic markers and therapeutic targets in glioblastoma.Discover oncology · 2026Article
- Cell death pathways and targeting therapeutics in cancer therapy.Acta pharmacologica Sinica · 2026Review
- Apolipoproteins L involvement in immunity.Journal of human immunity · 2026Review
- Therapeutic targeting of BCL-2 during CART cell production augments potency through non-apoptotic adaptive changes.Signal transduction and targeted therapy · 2026Article
- What does BCL-2 do? From new molecular insights to the clinical implications.Cell death and differentiation · 2026Review
- Inhibition of MAPK p38α overcomes the cancer immunosurveillance defect caused by FPR1 loss-of-function mutation.Cell reports. Medicine · 2026Article
- Neutralization of acyl-CoA-binding protein attenuates glucocorticoid-mediated suppression of cancer immunosurveillance.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- p21-Positive Senescent Stromal Cells Promote Prostate Cancer Immune Suppression and Progression That Can Be Reversed by Senolytic Therapy.Cancer discovery · 2026Article
- <p>Tumor microenvironment in bone sarcomas: Implications for immunotherapy and emerging therapeutic vulnerabilities (Review)</p>.Oncology reports · 2026Review
- Exploring the toxicological effects of Di-O-benzoyldiethylene glycol plasticizer on allergic rhinitis through network toxicology combined with molecular docking and molecular simulation.Scientific reports · 2026Article
- Dual Bcl-2/Bcl-xl inhibition via AZD0466 combines with immune checkpoint blockade to enhance anti-tumour activity.Cell death & disease · 2026Article
- Inosine alleviates colorectal cancer liver metastasis by promoting M1 macrophage polarization and modulating the PI3K/AKT signaling pathway.Frontiers in immunology · 2026Article
- ACBP/DBI Neutralization Stimulates Anticancer Immune Responses by Upregulating Lamin A in T Cells.ImmunoTargets and therapy · 2026Article
- Immunometabolic Rewiring of Dendritic Cells to Overcome Glutamine-Driven Immune Suppression in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Venetoclax as a trigger for autoimmune hemolytic anemia in secondary acute myeloid leukemia: A case report.SAGE open medical case reports · 2026Article
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Authors and funding
23 authors at 4 institutions in 5 countries.
Funding
Abstract
We developed a phenotypic screening platform for the functional exploration of dendritic cells (DC). Here, we report a genome-wide CRISPR screen that revealed BCL2 as an endogenous inhibitor of DC function. Knockout of BCL2 enhanced DC antigen presentation and activation as well as the capacity of DCs to control tumors and to synergize with PD-1 blockade. The pharmacologic BCL2 inhibitors venetoclax and navitoclax phenocopied these effects and caused a cDC1-dependent regression of orthotopic lung cancers and fibrosarcomas. Thus, solid tumors failed to respond to BCL2 inhibition in mice constitutively devoid of cDC1, and this was reversed by the infusion of DCs. Moreover, cDC1 depletion reduced the therapeutic efficacy of BCL2 inhibitors alone or in combination with PD-1 blockade and treatment with venetoclax caused cDC1 activation, both in mice and in patients. In conclusion, genetic and pharmacologic BCL2 inhibition unveils a DC-specific immune checkpoint that restrains tumor immunosurveillance. SIGNIFICANCE: BCL2 inhibition improves the capacity of DCs to stimulate anticancer immunity and restrain cancer growth in an immunocompetent context but not in mice lacking cDC1 or mature T cells. This study indicates that BCL2 blockade can be used to sensitize solid cancers to PD-1/PD-L1-targeting immunotherapy. This article is featured in Selected Articles from This Issue, p. 2293.
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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.