Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1320682 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Belantamab Mafodotin Triggers Immune Invigoration in Multiple Myeloma Via Inflammatory and Immunogenic Cell Death [Xenium]
| PRJNA1322471 | ENA
Project description:Belantamab mafodotin, an antibody-drug conjugate targeting B-cell maturation antigen, has demonstrated significant clinical efficacy in combination therapies for relapsed or refractory multiple myeloma. Belantamab mafodotin exerts therapeutic effects through the cytotoxic action of its payload, monomethyl auristatin F, along with its ability to mediate antibody-induced cell death. Significant long-term clinical responses were previously observed in monotherapy treatment – even in patients undergoing dose holds – suggesting involvement of the adaptive immune system. Here, we show that belantamab mafodotin induces markers of immunogenic and inflammatory cell death in vitro and ex vivo. Belantamab mafodotin monotherapy treatment results in an acute inflammatory response that is detectable in patient serum within 24 hours, with increases in granzyme B, CXCL9, CCL3, and CCL4 linked to response depth. High expression of receptors LRP1 and TLR2 that mediate immunogenic cell death on patients’ monocytoid (monocyte/macrophage) cells suggests an important function of the monocytoid lineage to mediate the observed inflammation and immunogenic cell death cascades. Inflammation is followed by remodeling of the innate and adaptive immune system, with a reduction in immune inhibitory signaling alongside the emergence of a CD4 granzyme B-expressing cell population in patients who are in remission vs those that relapse. The ability of belantamab mafodotin to promote adaptive immune responses in addition to its cytotoxic activity may help explain the durable responses observed in treated patients with relapsed/refractory multiple myeloma, despite dose and schedule modifications.
2025-09-14 | GSE307661 | GEO
Project description:Belantamab mafodotin, an antibody-drug conjugate targeting B-cell maturation antigen, has demonstrated significant clinical efficacy in combination therapies for relapsed or refractory multiple myeloma. Belantamab mafodotin exerts therapeutic effects through the cytotoxic action of its payload, monomethyl auristatin F, along with its ability to mediate antibody-induced cell death. Significant long-term clinical responses were previously observed in monotherapy treatment – even in patients undergoing dose holds – suggesting involvement of the adaptive immune system. Here, we show that belantamab mafodotin induces markers of immunogenic and inflammatory cell death in vitro and ex vivo. Belantamab mafodotin monotherapy treatment results in an acute inflammatory response that is detectable in patient serum within 24 hours, with increases in granzyme B, CXCL9, CCL3, and CCL4 linked to response depth. High expression of receptors LRP1 and TLR2 that mediate immunogenic cell death on patients’ monocytoid (monocyte/macrophage) cells suggests an important function of the monocytoid lineage to mediate the observed inflammation and immunogenic cell death cascades. Inflammation is followed by remodeling of the innate and adaptive immune system, with a reduction in immune inhibitory signaling alongside the emergence of a CD4 granzyme B-expressing cell population in patients who are in remission vs those that relapse. The ability of belantamab mafodotin to promote adaptive immune responses in addition to its cytotoxic activity may help explain the durable responses observed in treated patients with relapsed/refractory multiple myeloma, despite dose and schedule modifications.
2025-09-14 | GSE307660 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and is associated with a dismal prognosis. Due to late diagnosis, the disease is frequently locally advanced and not amenable to surgical resection, and only a small fraction of patients benefit from radio- or chemotherapy. Immunotherapy has shown limited efficacy as monotherapy, largely due to the profoundly immunosuppressive tumor microenvironment. Recent studies have demonstrated that anti-tumor immune responses can be elicited in pancreatic cancer through activation of the cGAS-STING and RIG-I-MAVS pathways, particularly in the context of radiation therapy. Notably, a hypofractionated radiation regimen of 3×8 Gy has been shown to be more effective than a single dose in inducing immunogenic cell death, type I interferon (IFN-I) signaling, and pro-inflammatory cytokine production. PARP7 inhibitors have also been reported to promote anti-tumor immunity by activating IFN-I responses in lung and colon cancer. Here, we show that in PDAC cells, PARP7 inhibition potentiates the effects of radiation by enhancing STING- and NF-κB dependent immunogenic signaling, inflammatory gene expression, pro-inflammatory cytokine release, immunogenic cell death, and immune cell activation. We performed RNA-seq analysis of all two PDAC cell lines treated with 3x8 Gy alone, or in combination with two different PARP7 inhibitors RBN-2397 and KMR-206.
2026-06-01 | E-MTAB-16549 | biostudies-arrayexpress
Project description:Halting Multiple Myeloma with MALT1 Inhibition: Suppressing BCMA-Induced NF-κB and Inducing Immunogenic Cell Death
| PRJNA1107568 | ENA
Project description:Napabucasin eliminates multiple myeloma through STAT3 inhibition-mediated stemness ablation and ER stress-induced immunogenic cell death
| PRJNA1272354 | ENA
Project description:PV-10 triggers immunogenic cell death in head and neck squamous cell carcinoma via endoplasmic reticulum stress and apoptosis
| PRJNA1225284 | ENA
Project description:Proteasome inhibitor bortezomib (BTZ) induces apoptosis in myeloma (MM) cells, and has transformed patient outcome. Using in vitro as well as in vivo immunodeficient and immunocompetent murine MM models, we here show that BTZ also triggers immunogenic cell death (ICD) characterized by exposure of calreticulin (CALR) on dying MM cells, phagocytosis of tumor cells by dendritic cells, and induction of MM specific immunity. We identify a BTZ-triggered specific ICD-gene signature which confers improved outcome in two independent MM patient cohorts. Importantly, BTZ stimulates MM cells immunogenicity via activation of cGAS/STING pathway and production of type-I interferons; and STING agonists significantly potentiate BTZ-induced ICD. Our studies therefore delineate mechanisms whereby BTZ exerts immunotherapeutic activity, and provide the framework for clinical trials of STING agonists with BTZ to induce potent tumor-specific immunity and improve patient outcome in MM.
2021-04-12 | GSE171837 | GEO
Project description:Signal transducer and activator of transcription 3 (STAT3) is a pivotal oncogenic driver in multiple myeloma (MM), where its constitutive activation promotes malignant plasma cell proliferation, survival, and drug resistance in the bone marrow microenvironment. Despite therapeutic advances, MM remains incurable due to persistent STAT3-driven tumorigenesis and the resilience of MM stem cells. Here, we investigated the therapeutic potential of Napabucasin (BBI608), a novel STAT3 inhibitor, in MM. Our data demonstrate that BBI608 potently suppresses MM cell proliferation in vitro and in vivo, while significantly impairing clonogenic potential and inducing robust apoptosis. Mechanistically, BBI608 exhibits dual efficacy by not only targeting bulk tumor cells but also eradicating the stem-like compartment of MM cells, addressing a critical therapeutic challenge. Moreover, we reveal that BBI608 triggers immunogenic cell death (ICD) via activation of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), which subsequently enhances T-cell-mediated anti-tumor immunity. Our findings underscore STAT3 inhibition as a promising strategy to simultaneously eradicate MM cells, target stem cell reservoirs, and harness anti-tumor immunity, providing a robust rationale for clinical translation of BBI608 in MM therapy.
2026-08-12 | GSE299035 | GEO
Project description:Pro-inflammatory cytokines were shown to promote growth and survival of cancerous cells. TNF induced RelA:p50 NF-κB dimer via the canonical pathway is thought to link inflammation with cancer. Integrating biochemical and computational studies we identify that deficiency of non-canonical signal transducer p100 triggers a positive autoregulatory loop, which instead perpetuates an alternate RelB:p50 containing NF-κB activity upon TNF treatment. TNF stimulated RelB:p50 dimer is sufficient for mediating NF-κB target gene-expressions and suppressing apoptotic cellular death independent of principal NF-κB subunit RelA. We further demonstrate that activating mutations in non-canonical NF-κB module deplete multiple myeloma cells of p100, thereby, provoking autoregulatory RelB:p50 activation. Finally, autoregulatory control reinforces protracted pro-survival NF-κB response, albeit comprising of RelB:p50, upon TNF priming that protects myeloma cells with dysfunctional p100 from subsequent apoptotic insults. In sum, we present evidence for positive autoregulation mediated through the NF-κB system and its potential involvement in human neoplasm.
2017-06-12 | GSE68615 | GEO