Cancer immunotherapy aims to activate the patient’s immune cells, in particular T cells, to kill and eradicate tumors. However, many cancer immunotherapies are made ineffective due to a number of tumor-intrinsic resistance mechanism: downregulation of the antigen processing and presentation machinery, upregulation of immune checkpoint molecules, dysregulated interferon signalling, tumor plasticity etc. Therefore, this project would aim at targeting epigenetically regulated pathways involved in immune escape with small molecular drugs to enhance recognition and killing of tumor cells by T-cells. These strategies also have a clear translational applicability for patients that are refractory to immunotherapies.

Master projects can be done in the following research lines:

1. To test anti-cancer drugs with diverse modes of action for their ability to sensitize tumors for recognition and killing by T cells. We have identified already drugs that show marked effects in this respect. A typical project for a master student would focus on finding out what molecular mechanisms cause these sensitizing effects.

2.To unravel mechanisms involving tumor epigenetics, cellular plasticity and immunogenicity in several solid tumors. Ultimately, we aim at blocking immunosuppressive pathways to enhance immune responses by T cells against tumors, with a focus on the differentiation status of tumor cells. A typical internship project would focus on inhibiting key pathways at the epigenetic level, and involved in differentiation of tumor cells.

Successful findings in these projects help create new strategies to increase the efficacy of immunotherapeutic treatments.