Publications by authors named "Shiv Bhuvane"
Differential outcomes of EphB4-ephrinB2 signaling offers formidable challenge for the development of cancer therapeutics. Here, we interrogate the effects of targeting EphB4 and ephrinB2 in head and neck squamous cell carcinoma (HNSCC) and within its microenvironment using genetically engineered mice, recombinant constructs, pharmacologic agonists and antagonists. We observe that manipulating the EphB4 intracellular domain on cancer cells accelerates tumor growth and angiogenesis.
View Article and Find Full Text PDFPurpose: Natural killer (NK) cells are type I innate lymphoid cells that are known for their role in killing virally infected cells or cancer cells through direct cytotoxicity. In addition to direct tumor cell killing, NK cells are known to play fundamental roles in the tumor microenvironment through secretion of key cytokines, such as FMS-like tyrosine kinase 3 ligand (FLT3L). Although radiotherapy is the mainstay treatment in most cancers, the role of radiotherapy on NK cells is not well characterized.
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- Research is focused on overcoming resistance to radiation therapy (RT) combined with immunotherapy in head and neck squamous cell carcinoma (HNSCC) using mouse models to understand the tumor microenvironment's response to treatment.
- Findings reveal that targeting traditional immunosuppressive myeloids is ineffective; instead, a combination of RT, Treg depletion, and anti-CD137 agonism enhances dendritic cell activation and reprograms Tregs, leading to a strong CD8 T cell response.
- Successfully increasing RT dosage and combining it with specific treatments results in tumor eradication, while high Treg levels in human oral squamous cell carcinoma are linked to quicker tumor recurrence, emphasizing the need to manipulate
Background: Resistance to therapy is a major problem in treating head and neck squamous cell carcinomas (HNSCC). Complement system inhibition has been shown to reduce tumor growth, metastasis, and therapeutic resistance in other tumor models, but has yet to be explored in the context of HNSCC. Here, we tested the effects of complement inhibition and its therapeutic potential in HNSCC.
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- Stromal fibrosis in pancreatic ductal adenocarcinoma (PDAC) activates pathways that promote survival and epithelial-to-mesenchymal transition (EMT), contributing to resistance to therapy and tumor invasion after radiation treatment.
- Research shows that after neoadjuvant stereotactic body radiation therapy (SBRT), there is an increase in fibrosis and specific gene signatures associated with EMT, implicating two proteins—ADAM10 and ephrinB2—as key players in tumor progression.
- Targeting ADAM10 can reduce RT-induced fibrosis and enhance tumor cell sensitivity to radiation, leading to increased survival in mouse models, suggesting new strategies to overcome radiation resistance in PDAC patients.