We have characterized the AP1 transcription factors c-Jun and JunB as an important transcription factor controlling pDC and DC development, activation and recruitment during TLR-induced responses. Thus, therapies that broadly target AP-1 signalling could adversely affect the DC compartment (Novoszel et. al. Cell Death and Diff., 2021)
We identified c-Jun/AP-1 to be a critical downstream effector of TLR-7 signalling in DCs by transcriptionally controlling the production of important inflammatory cytokines involved in psoriasis development (Novoszel e. al. EMBO Mol. Med. 2021).
We developed a novel strategy of in-situ tumor vaccination using a combination of oral and topical TLR7/8 agonists in preclinical models of melanoma and breast cancer. This treatment approach enhanced tumor-specific CD8+ immune response that was further potentiated by anti-PD1 blockade. (Sanlorenzo, Novoszel et al. in prep).
We identified gene expression signatures and pathways modulating/conferring tumor killing capacities to activated pDCs in preclinical samples. These signatures were shown to be predictive for increased survival in melanoma and SCC patients. (Gastaldi et al. in prep).
We have characterized EGFR positive macrophages for their basic physiological functions.
We have performed RNAseq analysis of liver TAMs and identified that several immunotimulatory cytokines were upregulated in TAMs lacking the EGFR (Robl, Matrone et. al. in prep).
In collaboration with M. Karin’s laboratory, we could also demonstrate an interaction between CD44 and EGFR during HCC formation (Dhar...Glitzner et. al, Cancer Cell 2018)
We have performed single cell RNAseq on mouse CRC and found that EGFR deletion in myeloid cells leads to changes within the immune infiltrate that relieve the immunosuppressive environment leading to lower tumor burden (Fari, Neuhofer, in prep).
We showed that inducible EGFR deletion in tumor cells of CRC does not impinge on tumor growth (Srivatsa, Paul et al. Gastroenterology, 2017).
We developed an organoid-based metastatic CRC model in mice which is based on using GEMMs lacking the EGFR in different cellular compartments transplanted orthotopically with syngeneic mouse CRC organoids carrying different oncogenic mutations. This system allows to study how oncogenic mutations in tumor cells affect the tumor microenvironment and vice versa (Moreno-Viedma, Fari, Neuhofer, in prep).
We have established a novel mouse model of HCC that is based on the intrasplenic injection of luciferase-transduced Hep55.1c cells that lead to HCC in 4 weeks.
We characterized human CRC samples, detected EGFR+ myeloid cells in these tumors and correlated their presence to a worse overall survival of metastatic patients (Srivatsa, Paul et al. Gastroenterology, 2017).
We could also correlate the presence of EGFR positive myeloid cells and the response of CRC patients to anti-EGFR treatment (Moreno-Viedma, Taghizadeh, Göcen in prep).
We performed RNASeq analysis on dissected tumor and stroma of CRC patients and characterized how mutations in tumors affect stromal signatures and vice versa (Moreno-Viedma, Mohr, in prep).
We found the receptor Axl to be overexpressed in the stroma of advanced CRC patients where it correlates with a worse survival in patients (Cardone, Blauensteiner, Eur J Cancer, 2020).
