ArticleBlood2014
TPL2 kinase regulates the inflammatory milieu of the myeloma niche.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- The Global Prevalence of Vitamin D Deficiency and Insufficiency in Patients with Multiple Myeloma: A Systematic Review and Meta-Analysis.Nutrients · 2023Pooled it
- IAP antagonists induce anti-tumor immunity in multiple myeloma.Nature medicine · 2016Trial
- Versican Proteolysis by ADAMTS: Understanding Versikine Expression in Canine Spontaneous Mammary Carcinomas.Cancers · 2024Article
- Emergency myelopoiesis in solid cancers.British journal of haematology · 2024Review
- An IL-1β-driven neutrophil-stromal cell axis fosters a BAFF-rich protumor microenvironment in individuals with multiple myeloma.Nature immunology · 2024Article
- Emerging roles for tumor stroma in antigen presentation and anti-cancer immunity.Biochemical Society transactions · 2023Review
- CK1δ and CK1ε Signaling Sustains Mitochondrial Metabolism and Cell Survival in Multiple Myeloma.Cancer research · 2023Article
- Exploring the potential of combining IL-2-activated NK cells with an anti-PDL1 monoclonal antibody to target multiple myeloma-associated macrophages.Cancer immunology, immunotherapy : CII · 2023Article
- Dissecting molecular mechanisms of immune microenvironment dysfunction in multiple myeloma and precursor conditions.Journal of cancer metastasis and treatment · 2023Article
- Refractory adult-onset Still's disease complicated with monoclonal gammopathy of undetermined significance: A case report.Medicine · 2022Article
- Targeting CAM-DR and Mitochondrial Transfer for the Treatment of Multiple Myeloma.Current oncology (Toronto, Ont.) · 2022Review
- Matrix proteoglycans in tumor inflammation and immunity.American journal of physiology. Cell physiology · 2022Review
- Stromal remodeling regulates dendritic cell abundance and activity in the tumor microenvironment.Cell reports · 2022Article
- Proceedings from the Blood and Marrow Transplant Clinical Trials Network Myeloma Intergroup Workshop on Immune and Cellular Therapy in Multiple Myeloma.Transplantation and cellular therapy · 2022Article
- Modulation of hyaluronan signaling as a therapeutic target in human disease.Pharmacology & therapeutics · 2022Review
- Deciphering mechanisms of immune escape to inform immunotherapeutic strategies in multiple myeloma.Journal of hematology & oncology · 2022Review
- Aiduqing formula inhibits breast cancer metastasis by suppressing TAM/CXCL1-induced Treg differentiation and infiltration.Cell communication and signaling : CCS · 2021Article
- Inhibition of miR-144/199 promote myeloma pathogenesis via upregulation of versican and FAK/STAT3 signaling.Molecular and cellular biochemistry · 2021Article
- BMI1 regulates multiple myeloma-associated macrophage's pro-myeloma functions.Cell death & disease · 2021Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Targeted modulation of microenvironmental regulatory pathways may be essential to control myeloma and other genetically/clonally heterogeneous cancers. Here we report that human myeloma-associated monocytes/macrophages (MAM), but not myeloma plasma cells, constitute the predominant source of interleukin-1β (IL-1β), IL-10, and tumor necrosis factor-α at diagnosis, whereas IL-6 originates from stromal cells and macrophages. To dissect MAM activation/cytokine pathways, we analyzed Toll-like receptor (TLR) expression in human myeloma CD14(+) cells. We observed coregulation of TLR2 and TLR6 expression correlating with local processing of versican, a proteoglycan TLR2/6 agonist linked to carcinoma progression. Versican has not been mechanistically implicated in myeloma pathogenesis. We hypothesized that the most readily accessible target in the versican-TLR2/6 pathway would be the mitogen-activated protein 3 (MAP3) kinase, TPL2 (Cot/MAP3K8). Ablation of Tpl2 in the genetically engineered in vivo myeloma model, Vκ*MYC, led to prolonged disease latency associated with plasma cell growth defect. Tpl2 loss abrogated the "inflammatory switch" in MAM within nascent myeloma lesions and licensed macrophage repolarization in established tumors. MYC activation/expression in plasma cells was independent of Tpl2 activity. Pharmacologic TPL2 inhibition in human monocytes led to dose-dependent attenuation of IL-1β induction/secretion in response to TLR2 stimulation. Our results highlight a TLR2/6-dependent TPL2 pathway as novel therapeutic target acting nonautonomously through macrophages to control myeloma progression.
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.