ArticleCancer immunology, immunotherapy : CII2013
A novel inhibitor of proteasome deubiquitinating activity renders tumor cells sensitive to TRAIL-mediated apoptosis by natural killer cells and T cells.
Article in Cancer immunology, immunotherapy : CII, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 31 citations in OpenAlex.
- b-AP15 enhances TRAIL-induced cell death in HNSCC via the induction of ROS/JNK/DR5 signalling.Cancer gene therapy · 2026Article
- Proteasomal deubiquitinating enzyme USP14/UCHL5 inhibitor bAP15 suppresses endoplasmic reticulum stress-mediated apoptosis and tumor growth in human chondrosarcoma.American journal of cancer research · 2025Article
- Ubiquitin modification in the regulation of tumor immunotherapy resistance mechanisms and potential therapeutic targets.Experimental hematology & oncology · 2024Review
- The UCHL5 inhibitor b-AP15 overcomes cisplatin resistance via suppression of cancer stemness in urothelial carcinoma.Molecular therapy oncolytics · 2022Article
- Genistein Sensitizes Human Cholangiocarcinoma Cell Lines to Be Susceptible to Natural Killer Cells.Biology · 2022Article
- The Biological Role and Therapeutic Potential of NK Cells in Hematological and Solid Tumors.International journal of molecular sciences · 2021Review
- Regulatory interplay between deubiquitinating enzymes and cytokines.Cytokine & growth factor reviews · 2019Review
- Review
- The Deubiquitinase Inhibitor b-AP15 and Its Effect on Phenotype and Function of Monocyte-Derived Dendritic Cells.Neoplasia (New York, N.Y.) · 2019Article
- Natural killer group 2D receptor and its ligands in cancer immune escape.Molecular cancer · 2019Review
- The novel deubiquitinase inhibitor b-AP15 induces direct and NK cell-mediated antitumor effects in human mantle cell lymphoma.Cancer immunology, immunotherapy : CII · 2018Article
- Synergistic effects of combining proteasome inhibitors with chemotherapeutic drugs in lung cancer cells.BMC research notes · 2017Article
- The proteasome deubiquitinase inhibitor b-AP15 enhances DR5 activation-induced apoptosis through stabilizing DR5.Scientific reports · 2017Article
- Coinhibition of the deubiquitinating enzymes, USP14 and UCHL5, with VLX1570 is lethal to ibrutinib- or bortezomib-resistant Waldenstrom macroglobulinemia tumor cells.Blood cancer journal · 2016Article
- USP14 is a predictor of recurrence in endometrial cancer and a molecular target for endometrial cancer treatment.Oncotarget · 2016Article
- The Deubiquitinase Inhibitor PR-619 Sensitizes Normal Human Fibroblasts to Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL)-mediated Cell Death.The Journal of biological chemistry · 2016Article
- Targeting the tumor microenvironment to improve natural killer cell-based immunotherapies: On being in the right place at the right time, with resilience.Human vaccines & immunotherapeutics · 2016Article
- NK cell-based immunotherapies in Pediatric Oncology.Journal of pediatric hematology/oncology · 2015Review
- Inhibition of 19S proteasome-associated deubiquitinases by metal-containing compounds.Oncoscience · 2015Review
- Trailing TRAIL Resistance: Novel Targets for TRAIL Sensitization in Cancer Cells.Frontiers in oncology · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The proteasome inhibitor bortezomib simultaneously renders tumor cells sensitive to killing by natural killer (NK) cells and resistant to killing by tumor-specific T cells. Here, we show that b-AP15, a novel inhibitor of proteasome deubiquitinating activity, sensitizes tumors to both NK and T cell-mediated killing. Exposure to b-AP15 significantly increased the susceptibility of tumor cell lines of various origins to NK (p < 0.0002) and T cell (p = 0.02)-mediated cytotoxicity. Treatment with b-AP15 resulted in increased tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor-2 expression (p = 0.03) and decreased cFLIP expression in tumor cells in vitro. In tumor-bearing SCID/Beige mice, treatment with b-AP15 followed by infusion of either human NK cells or tumor-specific T cells resulted in a significantly delayed tumor progression compared with mice treated with NK cells (p = 0.006), T cells (p < 0.0001) or b-AP15 alone (p = 0.003). Combined infusion of NK and T cells in tumor-bearing BALB/c mice following treatment with b-AP15 resulted in a significantly prolonged long-term survival compared with mice treated with b-AP15 and NK or T cells (p ≤ 0.01). Our findings show that b-AP15-induced sensitization to TRAIL-mediated apoptosis could be used as a novel strategy to augment the anticancer effects of adoptively infused NK and T cells in patients with cancer.
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.