New 'atlas' for dendritic cells creates order in international nomenclature
VUB-KUL researcher develops mouse model to study tumour development as well as interaction with the immune system and metastasis of ovarian cancer cells
For her PhD at VUB and KULeuven, Aarushi Caro, also at VIB, created a kind of systematics for dentritic cells, a special group of immune cells in the fight against cancer. Until now, there was a lot of confusion about the different types of dentritic cells. "Scientists worldwide use different names for similar cells, which makes it difficult to compare them," Caro explains. To address that problem, she used advanced techniques to map a comprehensive overview of dendritic cells in both mice and humans and across multiple cancer types
Dendritic cells act as the body's watchdogs: they detect abnormalities such as infections or cancer cells and then prompt other immune cells to take action. Yet research on these cells has long been hampered by a lack of clarity. "Many different descriptions and designations existed for dendritic cells, which made it difficult to compare studies," explains Aarushi Caro. Caro performed analyses of dentritic cells using single-cell RNA sequencing, an advanced technique that allows individual cells to be analysed in detail.
Based on this, she developed comprehensive 'atlases' of tumour-associated dendritic cells, both in mouse models and human cancers. These included data from 14 mouse models and 10 different cancer types in humans. The results show that many of the cells are very similar between species, although there also appear to be clear differences. Caro links specific types of dendritic cells to patients' survival rates. "That helps us better understand which immune responses are beneficial and which are less so," she says.
In the second part of her research, Caro zoomed in on ovarian cancer, a disease with a high mortality rate (up to 40 per cent). A major limitation in research and treatment is the lack of suitable preclinical models that realistically mimic the disease. Therefore, Caro developed a new orthotopic mouse model that goes through all stages of the disease, including advanced stages with metastases. "Existing models often evolve slowly and do not reach the stage we see in many patients at diagnosis," Caro said. Her model makes it possible to accurately study both tumour development and the interaction with the immune system and metastasis of cancer cells.
Using her model, she then tested different therapeutic strategies. On the one hand, she investigated vaccinations with tumour-associated dendritic cells, both preventive and therapeutic. On the other hand, she focused on an innovative approach with AXL-targeted nanobodies. AXL is a protein that is highly present in ovarian cancer and is associated with a worse prognosis. The study shows that the nanobodies can kill cancer cells directly," says Caro.
Aarushi Caro's PhD forms a coherent whole that runs from fundamental understanding of immune cells to concrete therapeutic applications. By better mapping the heterogeneity of dendritic cells, developing a robust and clinically relevant model and testing new treatments, her work makes a very valuable contribution to future cancer research. "Our goal is to eventually translate that knowledge into therapies that really benefit patients," she concludes.
Aarushi leaves at the end of this month for a postdoctoral adventure in the lab of Prof Shalin Naïk in Melbourne, a very big name in the dendritic-cell field.
More info:
Aarushi Caro: Aarushi.Audhut.Caro@vub.be (English-language)
For Dutch-language clarification: Damya Laoui: damya.laoui@vub.be
Exploring dendritic cell heterogeneity in tumours: From preclinical models to therapeutic applications
