Combined inhibition of S100A4 and TIGIT suppresses late-stage breast cancer metastasis to the lung by activating T and NK cells
Leu, J.-S.; Deng, H.; Tran, H. N.; Wei, X.; Hashiomoto, C.; Leonard, F.; Wong, T.; Abdelfattah, N.; Benitez Salazar, J. M.; Kang, R.; Maldonado, J. A.; Cristobal, C. D.; Lee, H. K.; An, Z.; Zhang, N.; Yun, K.
Show abstract
Cancer metastasis is responsible for approximately 90% of cancer-related deaths, but very few treatment options exist currently. While the role of S100A4 in promoting metastasis has been known for decades, this knowledge has not been translated in the clinic. Here, we report that a novel monoclonal antibody against the human S100A4 protein (S1004-11) effectively suppresses breast cancer metastasis in two different mouse models. Importantly, a novel combination of ant-TIGIT and S100A4-11 can suppress lung metastases even in late-stage disease after the lung premetastatic niche (PMN) has already been established similar to a stage when many breast cancer patients are diagnosed. Mechanistically, S1004-11 mAb treatment block the formation of PMN by suppressing neutrophil infiltration and activating natural killer (NK) and T cells in the lung. Single-cell RNA-sequencing and cell:cell communication analyses indicate that TIGIT signaling suppresses NK cells, which is reversed in S100A4-11 treated PMN. In summary, this study provides compelling evidence for a novel mechanism of S100A4 function in PMN formation and the feasibility of using S100A4-11 monoclonal antibody to suppress metastases at different stages of breast cancer progression.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Targeting EIF4A triggers an interferon response to synergize with chemotherapy and suppress triple-negative breast cancer 96%
- Tumor-educated Gr1+CD11b+ cells instigate breast cancer metastasis by twisting cancer cells plasticity via OSM/IL6-JAK signaling 96%
- SLIT2-ROBO signaling in tumor-associated microglia/macrophages drives glioblastoma immunosuppression and vascular dysmorphia 96%
Similar papers in this journal
- Inflammatory cytokines mediate the induction of and awakening from metastatic dormancy 96%
- Stromal remodeling regulates dendritic cell abundance and activity in the tumor microenvironment 96%
- An autophagy program that promotes T cell egress from the lymph node controls responses to immune checkpoint blockade 96%
Similar papers in this journal
- Vimentin is Required for Tumor Progression and Metastasis in a Mouse Model of Non-Small Cell Lung Cancer 95%
- A SNAI2-PEAK1 stromal axis drives progression and lapatinib resistance in HER2-positive breast cancer by supporting a cytokine expression profile that converges on PI3K/Akt signaling 95%
- FRA1 drives melanoma metastasis through an actionable transcriptional network 95%
Similar papers in this journal
Similar papers in this journal
- Therapeutic KRASG12C inhibition drives effective interferon-mediated anti-tumour immunity in immunogenic lung cancers 96%
- MLL1 regulates cytokine-driven cell migration and metastasis 96%
- Selective disruption of lipid peroxide homeostasis in intratumoral regulatory T cells by targeting FSP1 enhances cancer immunity 95%
"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.