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Institute of Experimental Immunology Tumorimmunology

Welcome to the van den Broek lab

Tumor Immunology van den Broek lab

 

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Understanding the mutual interaction between cancer and the immune system is the focus of the van den Broek lab. In particular, our dynamic, international team uses state-of-the-art basic research to understand how the immune system can be supported to control cancer in a sustainable way. We value team spirit, originality, intelligence, motivation and perseverance.

 

Van den Broek lab retreat 2022

Lab retreat, lake of Zurich, June 2022

Weiterführende Informationen

bioRxiv Preprint

Hakan Köksal and colleagues discovered that tumor-associated stem-like CD8+ T-cells proliferate and differentiate into effector CD8+ T-cells in response to radiotherapy. Thus, the presence of stem-like CD8+ T-cells in the tumor is a key determinant of therapeutic efficacy.

For more information, read our preprint:
https://www.biorxiv.org/content/10.1101/2024.10.16.618635v1

bioRxiv Preprint

Michael Herbst and colleagues discovered that STING signaling in CD8+ T-cells restricts their function and survival and thus, acts as a checkpoint that balances immunity in a cGAMP-rich environment such a tumor.

For more information, read our preprint:
https://www.biorxiv.org/content/10.1101/2024.10.28.620471v1

bioRxiv Preprint

Marc Nater and colleagues discovered an IL-4/IL-13-driven tumor-promoting function of iNKT cells in the early stages of liver metastasis, and thus established the mechanistic link between iNKT cells, fibrosis and liver metastasis.

For more information, read our preprint:
https://www.biorxiv.org/content/10.1101/2024.08.19.608250v1

bioRxiv Preprint

Paulo Pereira et al. discovered that interferon-gamma induces metastatic dormancy in the lungs and that IL-17A awakes dormant cancer cells again. Further, Paulo showed that for maintenance of dormancy, immune surveillance is dispensable.

For more information, read our preprint:
https://www.biorxiv.org/content/10.1101/2024.08.05.606588v1

Tertiary lymphoid structure in human bladder cancer

Initial steps of TLS development

Anna Laura Calvanese et al. discovered that type I interferon is an essential upstream mediator for development of tertiary lymphoid structures in the lungs. IFNAR1 signaling results in production of LTa, which in turn induces the B-cell attractant CXCL13. Further, IFNAR1 signaling induces T-cell attracting chemokines independently of LTbR signaling.

Full article: Sustained innate interferon is an essential inducer of tertiary lymphoid structures

Tertiary lymphoid structure in human bladder cancer (Karina Silina)

Tertiary lymphoid structure in human bladder cancer (Karina Silina)

 

Pagliarulo et al. describe the prognostic relevance of B-cells, CD8+ T-cells and tertiary lymphoid structures in muscle-invasive bladder cancer.

 

Full article: 2022 Pagliarulo Frontiers Imm.pdf

Our recent review summarizes the current knowledge and understanding of how CD8+ T-cells influence metastatic outbreaks and dormancy.

 

Full article: Anti-Metastatic Defense by CD8 T Cells.pdf

 

hepatic innate lymphocytes

Ducimetière, Lucchiari at al discovered that hepatic innate lymphocytes cooperate in a non-redundant fashion to control liver metastasis.

https://www.pnas.org/content/118/27/e2026271118

Illustration by Giulia Lucchiari.

Immunofluorescent image of a single, dormant breast cancer cell (red) disseminated to the lung (courtesy Héctor Castañón)

Many breast cancer patients suffer metastatic relapses years/decades after surgery. The cause are disseminated cancer cells that have become dormant. Paulino Tallón de Lara, Héctor Castañón et al. discovered that dormancy is induced by an anti tumor-immune reaction mediated by PD-1+ CD39+ CD8+ T-cells. Read more about this fantastic work here: https://www.nature.com/articles/s41467-021-21045-2

Preoperative ipilimumab plus nivolumab in locoregionally advanced urothelial cancer: the NABUCCO trial s41591-020-1085-z

 

van Dijk, Silina, et al. discovered that immune checkpoint inhibition also works in patients with bladder cancer whose tumors show little CD8+ T-cell infiltration and tertiary lymphoid structures before therapy. These parameters increased specifically in responders.