Multiscale Modeling Uncovers Macrophage Infiltration and TNF-α Signaling Networks for Targeting in Inflammatory Breast Cancer Tumor Emboli
PAI, P.; Van Berckelaer, C.; Van Laere, S.; Bennion, A.; Charity, T.; Yang, J.; Bertucci, F.; Van Dam, P.; Palmer, G. M.; McCall, S.; Dirix, L. Y.; Ueno, N. T.; Devi, G.
Show abstract
Inflammatory breast cancer (IBC) tumors are characterized by diffuse clusters of cells found in dermal tissue and lymphatic vessels, known as tumor emboli. Thus, IBC needs a novel treatment because it is the most aggressive breast cancer subtype. We hypothesized that the interaction between tumor emboli and the tumor immune microenvironment (TiME) fosters survival signaling, leading to the aggressiveness of the IBC. In this study, ex vivo tumor emboli were generated from patient-derived cell lines cultured in a lymphatic-like environment, which was compared to 2D monolayer cultures, revealing upregulation of TNFR signaling networks, CXCL8, and immune cell chemotaxis genes. Spatial immunophenotyping of IBC patient tumors demonstrated high levels of CD163+ tumor-associated macrophages (TAMs). Furthermore, intravital imaging of CX3cr1GFP mice confirmed macrophage movement toward tumor cell clusters. Finally, targeting macrophage-associated TNF--signaling using Birinapant, a SMAC mimetic, inhibited the tumor emboli phenotype in vivo, identifying Birinapant as a potential therapeutic agent to disrupt this signaling axis.
Matching journals
The top 13 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Vascularized tumor on a microfluidic chip to study mechanisms promoting tumor neovascularization and vascular targeted therapies 95%
- The molecular landscape and microenvironment of salivary duct carcinoma reveal new therapeutic opportunities 94%
- Focused ultrasound ablation of melanoma with boiling histotripsy yields abscopal tumor control and antigen-dependent dendritic cell activation 93%
Similar papers in this journal
- Nicotinamide combined with gemcitabine is an immunomodulatory therapy that restrains pancreatic cancer in mice 95%
- Reversible Downregulation of HLA Class I in Adenoid Cystic Carcinoma 95%
- Effector T Cells under Hypoxia have an Altered Transcriptome Similar to Tumor-Stressed T Cells Found in Non-Responsive Melanoma Patients 95%
Similar papers in this journal
- Propagated circulating tumor cells uncovers the rople of NFκB and COP1 in metastasis 95%
- Functionally and metabolically divergent melanoma-associated macrophages originate from common bone-marrow precursors 94%
- HIF-dependent expression of creatine kinase brain isoform (CKB) promotes breast cancer metastasis, whereas cyclocreatine therapy impairs invasion and improves the efficacy of conventional chemotherapies 93%
Similar papers in this journal
- Simulating the human tumor microenvironment in colorectal cancer organoids in vitro and in vivo 95%
- Proteogenomic Characterization of Triple-Negative Apocrine Carcinoma Reveals Molecular Features of Progression and Chemotherapy Response 94%
- Long-term maintenance of patient-specific characteristics in tumoroids from six cancer indications in a common base culture media system 94%
Similar papers in this journal
- Platinum chemotherapy induces lymphangiogenesis in cancerous and healthy tissues that can be prevented with adjuvant anti-VEGFR3 therapy 95%
- ERK3/MAPK6 promotes triple-negative breast cancer progression through collective migration and EMT plasticity 95%
- A dual readout embryonic zebrafish xenograft model of rhabdomyosarcoma to assess clinically relevant multi-receptor tyrosine kinase inhibitors 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.