The principle of cancer immunoediting allows a deeper understanding of the dual action of immunity on cancer. Whereas the immune system can detect and destroy transformed cells, the constant immune pressure evokes sculpting of the tumour that eventually leads to immune escape. During cancer immunoediting, the host immune system shapes the tumour in three consecutive steps. (i) In the elimination phase, malignant cells are destroyed by a competent immune system. (ii) Tumour cells that manage to survive immune cell-mediated destruction enter an equilibrium phase characterized by sculpting and editing of individual cell clones. (iii) In the escape phase, the edited tumours, which are refractory to immune cell eradication, start to grow and become clinically apparent.
In recent years, novel anti-cancer therapies have reached clinics and shown promising results. In particular, the clinical application of NK and T cells against cancer is an area of extensive investigation. However, we are still facing challenges caused by resistance to therapy and secondary metastasis. The combination of single-cell tracking by DNA barcoding and next-generation sequencing will enable a deeper understanding of the mutational landscape of tumours. The identification of basic mechanisms underlying tumour immune escape is of utmost importance to find novel therapeutic targets that show sustained success.
We aim to…
- quantify the process of NK cell-mediated leukaemia immunoediting.
- identify the molecular signature of NK cell-resistant tumour cell clones.
- find novel therapeutic targets to increase the immunogenicity and susceptibility of tumour cells towards NK cell-mediated surveillance.
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Stand-Alone Project (P32001-B) funded by the Austrian Science Fund (2019-2021).