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Dendritic cells (DCs) are incredible immune cells with the capacity to instruct T cells how to fight cancer. Scientists have recently discovered a new kind of DC, called DC3, that is found in the blood and tumors of cancer patients. In the context of cancer DC3s are compromised in activating other immune cells, and they may help cancer cells escape from the immune system.
In this research, Anouk Becker, Martijn Verdoes, Jolanda de Vries and collaborators from the (former) department of Tumor Immunology and Medical Imaging, set out to understand the origin and behavior of DC3s in melanoma and lung cancer. They found that lung cancer patients have more DC3s in their blood than healthy individuals, and removing the tumor restored DC3 frequencies back to normal. Further laboratory experiments with melanoma and lung cancer cells showed that tumor cells produce factors that convert a more effective cancer-fighting DC, known as DC2, into DC3s. The researchers were able to halt the development of DC3s by inhibiting the identified factors, IL-6 and M-CSF, using drugs already available in the clinic for other cancer types.
This study reveals one of the many ways cancer can manipulate the immune system. By targeting the factors that lead to DC3 formation, the immune system’s natural ability to fight cancer can be boosted. The researchers hope that these findings will contribute to the improvement of DC-based vaccines and other immunotherapies.
The results of this study have been published in Cell Reports Medicine on January 18, 2024 and can be found here.
Anouk M D Becker, Annika H Decker, Georgina Flórez-Grau, Ghaith Bakdash, Rutger J Röring, Suzan Stelloo, Michiel Vermeulen, Berber Piet, Erik H J G Aarntzen, Martijn Verdoes, I Jolanda M de Vries. Inhibition of CSF-1R and IL-6R prevents conversion of cDC2s into immune incompetent tumor-induced DC3s boosting DC-driven therapy potential. Cell Reports Medicine 5, 101386 February 20, 2024;
