Project objective

Scientific background:

Immuno-oncology is one of the fastest developing research areas in tumor biology and therapy. In the last years the development of different immunotherapy strategies, including therapies based on antibodies blocking immune checkpoints (in other words costimulatory receptors with suppressive functions) has brought a breakthrough in cancer therapy. The aim of these therapies is to boost an effective anti-tumor response and to overcome the immunosuppression induced by tumor cells. However very heterogeneous and hardly predictable response to this kind of treatments is a problem, which can be solved by the identification of appropriate prognostic biomarkers.

Our own previous studies as well as studies from other researchers point out the key role of extracellular vesicles (EVs) or exosomes, small membrane vesicles released by different cell types, in the modulation of anti-tumor response. EVs are the key elements of intercellular communication within the tumor microenvironment, carriers of genetic material and functional suppressive molecules derived from the tumor and essential mediators of local and systemic immune suppression. They impact the invasiveness of cancer cells and tumor metastasis, increase tumor-promoting angiogenesis and induce drug resistance. Since tumor-derived EVs contain tumor antigens and tumor markers on their surface, they may be used for diagnosis as so called “liquid biopsies” or may serve as biomarkers for prognosis or treatment response.

In a recently finished OPUS6 project financed by the National Science Center (NCN) MUW researchers have shown an immunosuppressive role of EVs in ovarian cancer. Now they run an OPUS14 project, where they investigate EVs from bronchoalveolar lavage fluid as potential biomarkers of the impairment of anti-tumor immune response in non-small cell lung cancer. Two other planned research projects will elucidate the impact of metabolites of tumor cells on exocytosis and vesicle secretion in NK cells and T lymphocytes and the impact of EVs on immune therapies with monoclonal antibodies.