Translation of CMV induced innate immunity into anti-cancer immune therapies

An allogeneic stem cell transplantation (allo-SCT) is often the best curative option for patients with poor risk hematological malignancies. However, it is associated with high toxicity and mortality, due to factors as Graft versus host disease (GvHD) and infections. Furthermore, some patients relapse after allo-SCT. In the UMCU, allo SCTs are T cell depleted, which can be done both ex vivo and in vivo. The rationale behind this is that by removing the αβ T cells the chance of developing GvHD disease decreases, while the innate immune system can still protect the patient against infections and relapse. Previously collected data suggest that the first week and months after transplantation the recovering immune system mainly consists of γδ T cells and NK cells. γδ T cells can be of importance in the 'Graft versus Leukemia' (GvL) effect. However, it is not yet fully understood which subsets of γδ T cells are most important in inducing tumor reactivity and which co-receptors might play a role. This project will particularly focus on the effect of CMV reactivation on the subsets of γδ T cells, as it has been shown that CMV reactivation causes a major increase in specific subsets. This is of importance, as it has also been shown that these specific subsets can recognise both CMV infected and malignant cells. In this project we will examine the diversity of γδ by both immunophenotyping and by single cell RNA sequencing (scRNAseq), while in the process developing tumor reactive clones. Our hypothesis is that immune reconstitution is faster in patients with CMV reactivation compared to patients who do not have CMV reactivation, and that these cells might contribute to the GvL effect.

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Anniek Stuut