Our Science

The immune suppressive tumor microenvironment drives tumor growth, therapy resistance & metastasis but is complex and multi-factorial. This calls for novel therapeutic strategies that target the tumor stroma from a different angle.

As such, high macrophage infiltration often correlates with immune suppression and macrophage targets are considered the next frontier in immuno-oncology. Perivascular macrophages (PVMs), a subclass of macrophages, are often overlooked in this context. Nonetheless, these PVMs cuff the vasculature and thereby sustain both immune suppression and dysfunction of the tumor vasculature.

The latter is a hallmark of cancer that is underappreciated in current therapies, but by hampering proper immune cell infiltration and tumor oxygenation, vascular dysfunction actively contributes to the malignant immunosuppressive microenvironment in tumors.

Historical therapies targeting the tumor vasculature largely ignored this role and instead destroyed the vessels to starve the tumor. Our research now shows that rather than destroying the blood vessels, we can use them to herd the correct immune cells to the tumor and get more potent and sustainable effects.

It is becoming increasingly clear that the interaction of endothelial cells (the inner cells lining the blood vessels) with PVMs shapes this multi-factorial immune suppressive response and that targeting this interaction can restore this environment.

Our approach with single cell RNA sequencing data finally allowed us to investigate the communication between PVMs & tumor endothelial cells and using our unique target screening platform, we discovered novel targets to translate this concept into a first-in-class therapeutic pipeline.