Similar to their normal tissue stem cell counterpart, cancers have been shown to contain a subset of so called cancer stem cells (or tumor initiating cells) that have the unique ability to perpetuate tumor growth and heterogeneity in serial transplantation experiments. Initially identified in leukemia, they have been subsequently described in a variety of solid cancers like glioblastoma, breast, colorectal, liver, prostate, and pancreatic cancer. CSCs are often rare within the tumor cell mass and, in addition, notoriously resistant against chemotherapeutic agents as well as radio- and immunotherapy. Accordingly, CSCs are thought to be the main cause of recurrence, even many years after patients were clinically staged as tumor-free. For example in breast cancer, recent results have demonstrated the important role of CSCs for metastatic spread which is still the main cause of cancer-related deaths. It is now well accepted that future therapy will have to consider this cancer cell subpopulation and, indeed, first attempts to specifically target CSCs have shown promising results.

Metastasis formation is cause of cancer-related death in over 90% of patients. However, our knowledge on how metastases initiate and grow is still rather limited. Surprisingly, it has been observed in experimental models that metastasis formation is a rather inefficient which likely reflects an inappropriate communication between tumor cells and the local microenvironment at a distant location in contrast to the primary site in which the tumor has initially evolved. Only a few disseminated tumor cells might be able to cope with the new environment. Our research aims to identify such restrictive mechanisms in order to develop preventive treatment strategies.

Enhancing immune activity against cancer is an attractive approach which combines specificity and multi-dimensional targeting. Immunotherapy holds several advantages over conventional therapies. First, immunotherapy often results in better controllable side effects, enabling it to be administered for longer periods of time. And because of the immune system’s ability to target multiple cancer antigens simultaneously, patients may also be less likely to develop resistance. Checkpoint blockade has been established as an immunotherapy with encouraging results in different cancer types. However, still a majority of patients does not show benefit from this type of treatment indicating that current strategies may miss several important mechanisms of immune evasion. One aspect which has not been sufficiently considered is how subpopulations of cancer cells and in particular cancer stem cells (CSCs) respond to immunotherapy. CSCs have the unique ability to perpetuate tumor growth and to initiate metastasis formation and we are working to improve immunotherapies targeting this highly relevant population of cancer cells.