Immune Treatments of Solid Tumors and T Cell Monitoring

To date there is no tool available to select patients for immunotherapies as there is a lack of markers that robustly predict therapy outcome or provide sufficient understanding into the underlying mechanisms that define unsuccessful treatment or toxicity. It is of pivotal importance to obtain such markers, since this will lead to improved stratification of patients for immune therapy. Patient stratification can prevent unnecessary treatment and increase cost-effectiveness of these treatments. To discover predictive markers, extensive monitoring of immunological as well as clinical parameters within clinical trials is mandatory.

This thesis is split into two parts.
In the first part, we have focused on immune monitoring tools in a CAR T cell phase-I trial to find parameters that correlate with in vivo behavior of administered T cells.
In the second part, we have monitored changes in T cells numbers, T cell clonality (number of different TCRs) and T cell phenotype in the blood compartment in patients receiving Dendritic Cell therapy in a phase-I trial. In addition, we have assessed the characteristics of intratumoral T cells in several soft tissue sarcoma (STS) subtypes in order to identify new parameters for immune monitoring in these tumor types.