Lunch Talk Series with Máté Kiss – Regulation of functionally distinct neutrophil states in cancer

Our upcoming Lunch Talk will be hosted by Stefanie Bärthel, Group Leader (Team NST) from BioMed X, and will feature Máté Kiss, Postdoctoral researcher in the field of cancer immunology at the AGORA Cancer Research Center in Lausanne, Switzerland.

• Topic: Regulation of functionally distinct neutrophil states in cancer.
• Location: DKFZ Communication Center, Im Neuenheimer Feld 280, Heidelberg.

Lunch Talk Description:

Neutrophils are among the most abundant innate immune cell types in the body and represent a first line of defense against pathogens. They can also kill cancer cells and stimulate anti-tumor immune responses, yet neutrophils frequently acquire tumor-promoting functions instead. The mechanisms controlling this switch from anti-tumor to pro-tumor neutrophil function remain poorly understood.

By analyzing the neutrophil compartment during cancer immunotherapy, we found that immunotherapy leads to a rapid, systemic expansion of a distinct neutrophil state with high expression of cytotoxic and interferon-stimulated genes. Emergence of these therapy-elicited neutrophils depends on the transcription factor IRF1 and is necessary for treatment success. These findings highlight the therapeutic value of beneficial neutrophil states in cancer and raise new questions about how this neutrophil response could be further enhanced.

In addition, our ongoing research aims to understand how tumor-promoting neutrophils arise. By profiling the epigenomic landscape of tumor-infiltrating neutrophils from both cancer patients and mouse models, we identified candidate transcription factors that control the function of these cells. Using a combination of CRISPR/Cas9-based genetic perturbations in neutrophils and experiments in neutrophil-specific conditional knockout mice, we identified a key transcription factor that drives the acquisition of a pro-tumorigenic neutrophil state.

In conclusion, our findings reveal pathways controlling neutrophil plasticity and nominate potential therapeutic targets to modulate neutrophil function in cancer.

About Máté Kiss:

Máté Kiss obtained his medical degree from the University of Debrecen, Hungary, and completed his PhD in cancer immunology at the Free University of Brussels, Belgium. He is currently a postdoctoral researcher in the field of cancer immunology at the AGORA Cancer Research Center in Lausanne, Switzerland, and an incoming junior group leader at the Georg-Speyer-Haus Institute for Tumor Biology and Experimental Therapy in Frankfurt, Germany.

His research explores how innate immune cells interact with cancer, aiming to identify the molecular mechanisms that regulate the function of these cells and to leverage this knowledge for cancer therapy.