Mie Wolff Kristensen

Since the introduction of combination immunotherapy and TKIs, treatment outcomes for mRCC patients have improved markedly with a subset of patients achieving durable or complete responses. Despite these results, a large group of patients do not respond to treatment, and therefore, selecting the right treatment for the right patient is crucial. Treatment selection is currently based on the IMDC prognostic criteria, but improvement is still needed due to large and heterogeneous prognostic groups.

The reason for treatment failure can likely be found in the tumor immune microenvironment (TIME), which comprises both  cancer cells, stromal cells, and a diverse composition of immune cells. Presence of tumor associated macrophages (TAMs) in the tumor, especially TAMs expressing CD163, is a poor prognostic factor in several cancers, and TAMs are abundant in RCC. Receptors such as CD163 can be shed from the surface of the cells and can be found in a soluble form in the blood.

Considering the improved survival after introduction of immunotherapy, the expression of different checkpoint molecules on immune cells could also be potential biomarkers. Generally, naïve immune cells rarely express high levels of checkpoint molecules, and while the expression increases after activation, further increase in expression is observed when cells become exhausted.

Preliminary data from two mRCC cohorts indicate that soluble macrophage markers and expression of immune checkpoint molecules hold potential as biomarkers, but they still need validation in a patient cohort receiving up to date first line treatment, which is planned as a part of the NORDIC SUN trial (NCT03977571).  This will hopefully improve our ability to select the right treatment for the right patient in the future.

CBZ-NOR-000233 05 2025