ArticleBlood2014
CD28-mediated pro-survival signaling induces chemotherapeutic resistance in multiple myeloma.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
What it found
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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.
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Who cites it
60 citing papers in PubMed, 89 citations in OpenAlex.
- Immunomodulatory effect of DC/CIK combined with chemotherapy in multiple myeloma and the clinical efficacy.International journal of clinical and experimental pathology · 2015Trial
- Targeting CD28 on T lineage malignancies with chimeric antigen receptor T cells.Nature communications · 2026Article
- Endogenous CD28 takes the driver's seat in 4-1BB co-stimulated CAR T cells.Molecular therapy. Oncology · 2026Article
- CD40LG/CD28-Mediated Rho GTPase Signaling Drives Survival and Chemoresistance in Non-ETP T-ALL.International journal of molecular sciences · 2026Article
- Endogenous CD28 Drives the Persistent Activity of CAR T Cells in Myeloma and Lymphoma Models.Blood cancer discovery · 2026Article
- Gut Microbiota-Immune Interactions in Endometrial Cancer: Causal Mediation and Subtype-Specific Mechanisms.International journal of women's health · 2026Article
- Why are long-lived plasma cells long-lived?Frontiers in immunology · 2026Review
- Pro-survival signaling regulates lipophagy essential for multiple myeloma resistance to stress-induced death.Cell reports · 2024Article
- Endogenous CD28 drives CAR T cell responses in multiple myeloma.bioRxiv : the preprint server for biology · 2024Article
- Immunophenotypic profile defines cytogenetic stability and unveils distinct prognoses in patients with newly-diagnosed multiple myeloma (NDMM).Annals of hematology · 2024Article
- Article
- Advancements in microenvironment-based therapies: transforming the landscape of multiple myeloma treatment.Frontiers in oncology · 2024Review
- Dysregulation of Non-Coding RNAs: Roles of miRNAs and lncRNAs in the Pathogenesis of Multiple Myeloma.Non-coding RNA · 2023Review
- BRF2 is mediated by microRNA-409-3p and promotes invasion and metastasis of HCC through the Wnt/β-catenin pathway.Cancer cell international · 2023Article
- Heterogeneity of B cell lymphopoiesis in patients with premalignant and active myeloma.JCI insight · 2023Article
- In good times and in bad: How plasma cells resolve stress for a life-long union with the bone marrow.Frontiers in immunology · 2023Article
- Dissecting molecular mechanisms of immune microenvironment dysfunction in multiple myeloma and precursor conditions.Journal of cancer metastasis and treatment · 2023Article
- Involvement of Small Non-Coding RNA and Cell Antigens in Pathogenesis of Extramedullary Multiple Myeloma.International journal of molecular sciences · 2022Article
- PDZ Proteins SCRIB and DLG1 Regulate Myeloma Cell Surface CD86 Expression, Growth, and Survival.Molecular cancer research : MCR · 2022Article
- CD24 Is a Prognostic Marker for Multiple Myeloma Progression and Survival.Journal of clinical medicine · 2022Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Chemotherapeutic resistance remains a significant hurdle in the treatment of multiple myeloma (MM) and is significantly mediated by interactions between MM cells and stromal cells of the bone marrow microenvironment. Despite the importance of these interactions, the specific molecules and downstream signaling components involved remain incompletely understood. We have previously shown that the prototypic T-cell costimulatory receptor CD28, which is also expressed on MM cells, is a key mediator of MM survival and apoptotic resistance. Crosslinking CD28 by agonistic antibodies or myeloid dendritic cells (DC; these express the CD28 ligands CD80/CD86) prevents apoptosis caused by chemotherapy or serum withdrawal. We now report that CD28 pro-survival signaling is dependent upon downstream activation of phosphatidyl-inositol 3-kinase/Akt, inactivation of the transcription factor FoxO3a, and decreased expression of the pro-apoptotic molecule Bim. Conversely, blocking the CD28-CD80/CD86 interaction between MM cells and DC in vitro abrogates the DC's ability to protect MM cells against chemotherapy-induced death. Consistent with these observations, in vivo blockade of CD28-CD80/CD86 in the Vk*MYC murine myeloma model sensitizes MM cells to chemotherapy and significantly reduces tumor burden. Taken together, our findings suggest that CD28 is an important mediator of MM survival during stress and can be targeted to overcome chemotherapy resistance.
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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.