The vascular immune cell axis in cancer

Summary: Tumors are often portrayed as wounds that do not heal because they undergo continuous stromal remodeling and vascular growth, with immunosuppressive features displaying characteristics of the proliferative resolution phase in the wound repair process. Indeed, the onset of angiogenesis and escape from immunosurveillance are not only described as hallmarks of cancer but also functionally inter-regulated, enabling tumor propagation and progression. One of our primary endeavors is to understand and therapeutically manipulate the heterogeneous communication between the endothelium and the different immune cells in a heterogeneous tumor cell compartment to awaken an immune-stimulating phase in the “tumor wound” with the final goal to eliminate tumor cells and invigorate tissue homeostasis.

Over the last years, my group has used various approaches to target the communication between the tumor vasculature and immune cell constituents and thereby identified several intimate regulatory mechanisms between angiogenesis and immunosuppression that provide novel target possibilities to enhance the effects of cancer therapy by modulating the tumor vascular system, e.g., by inducing high endothelial venules and tertiary lymphoid structures, and enhance immunity in a broader patient population to thwart tumors and metastases.

Hua, Y., Vella, G., Rambow, F., Allen, E., Martinez, A.A., Duhamel, M., Takeda, A., Jalkanen, S., Junius, S., Smeets, A., Nittner, D., Dimmeler, S., Hehlgans, T., Liston, A., Bosisio, F.M., Floris, G., Laoui, D., Hollmén, M., Lambrechts, D., Merchiers, P., Marine, J-C, Schlenner, S., Bergers, G. (2022). Cancer immunotherapies transition endothelial cells into high-endothelial venules that generate TCF1+ T lymphocyte niches through a feed-forward loop. Cancer Cell, 40(12):1600-1618.

Vella G, Hua Y and Bergers G. (2023). High endothelial venules in cancer: regulation, function and therapeutic implication. Cancer Cell

Allen, E., Jabouille, A., Rivera, L.B., Lodewijckx, I., Missiaen, R., Steri, V., Feyen, K., Tawney, J., Hanahan, D., Michael, I.P. and Bergers, G. (2017). Combined antiangiogenic and anti-PD-L1 therapy stimulates tumor immunity through HEV formation. Sci Transl Med 9 (385)

Rivera, L.B., Meyronet, D., Hervieu, V., Frederick, M.J., Bergsland, E., and Bergers, G.(2015). Intratumoral myeloid cells regulate responsiveness and resistance to antiangiogenic therapy. Cell Rep 11, 577-591

Biography: Gabriele Bergers is a Professor of Oncology at the University of Leuven and a group leader at the Vlaams Instituut voor Biotechnologie (VIB)-Center for Cancer Biology in Leuven since 2016. Before her move to the VIB, she was a Professor in the Department of Neurological Surgery and a PI in the Brain Tumor Research Center (BTRC) at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, for over 20 years. She has made seminal discoveries about perivascular tumor niches regarding the vasculature and the immune cell compartment in regulating neovascularization, inflammation, and TLS formation in cancer and in revealing and understanding intrinsic and evasive resistance mechanisms of tumors to antiangiogenic immunotherapies. Dr. Bergers has received several awards, including the Sidney Kimmel, the Sandler Opportunity, UCSF Breakthrough Biomedical Research, and the Judah Folkman. She is a panel member of grant institutions, including CPRIT, ERC, AIRC, and CRUK. She has acted as an external advisory board member for a number of universities and pharmaceutical companies and currently serves on the advisory board for Mestag Therapeutics. Dr. Bergers was the co-director of the Tumor Microenvironment Brain Tumor Center at UCSF and an advisor to the Max-Planck-Institute for Biomedicine in Muenster, Germany. She was a scientific co-founder of Oncurious.

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