DR-261 Chromosomal instability as key regulator of the immune microenvironment of cancers

Immune cells in the microenvironment of cancers impact disease progression and response to both conventional therapies and immune checkpoint blockers. Accumulating evidence indicates that genomic instability impacts the anti-tumor immune response; while microsatellite instability and mutational burden are associated with an inflamed immune microenvironment, chromosomal instability seems to be associated with immune cell exclusion. To explore this we aim to use genomic (copy numbers, somatic mutations) and microenvironmental (RNA) data to find interactions between genomic instability and the immune response, specifically using a novel measure of chromosomal instability that we recently developed (Van Dijk et al, 2021). Furthermore we aim to explore the feasibility of genomic and microenvironmental measures to predict the course of the disease and calculate associations with clinical parameters such as patient survival. Furthermore, we aim to identify groups of patients based on characteristics of genomic instability, and chromosomal instability (CIN) in particular, that respond better or worse to immune-activating agents.

Sarah Derks, VU Medical Center, Amsterdam UMC, the Netherlands