| Abstract [eng] |
Over the past decades, the tumor immunology and immunotherapy have revolutionized the clinical oncology. However, there are still challenges to overcome in understanding and targeting the immune elements of the tumor. In this thesis, the crosstalk of cancer and the immune system during the processes of tumor development and response to treatment was examined at local and systemic levels. First, the co-culture of cancer and immune cells revealed that stem-like cancer cells polarize macrophages towards the tumor-promoting phenotype, while macrophages upregulate the mesenchymal and stemness-related transcriptional profile in cancer cells. Second, the high tumoral ratio of immunosuppressive myeloid cells to antitumor myeloid cells appeared to be a marker of insensitivity to checkpoint blockade with anti-CTLA-4 and anti-PD-1 in iBIP2 mouse model of BRAF-mutated melanoma. Third, high preoperative levels of circulating CCL4+CCL20+CXCL1 chemokine combination in high-grade serous ovarian carcinoma patients were shown to predict the recurrence of the disease, while high preoperative levels of circulating CXCL9+CXCL10 chemokines could distinguish immune-infiltrated tumors. Overall, this study provides the evidence for the elements of the immune system to be actively involved in shaping the tumor microenvironment and serving as predictive biomarkers or therapeutic targets. |
