Natural killer cells in the tumor microenvironment: Enhancing immunotherapy by exploring the communication between NK cells and tumor cells

Every day, millions of people are confronted with the challenges of cancer, a disease that, despite advances in treatments, still has a significant mortality rate. This thesis investigates natural killer cell immunotherapy as a promising strategy that harnesses the natural ability of these NK cells to kill tumour cells. One of the findings of this research was the potential of combination therapy with NK cell-stimulating antibodies, which enhanced the activation of NK cells against resistant tumours. Furthermore, it was demonstrated that NK cells from genetically matched donors may be less effective than those from mismatched donors. These approaches were studied in various cancer models, including an innovative model in which the effectiveness of NK cells against patient-derived tumour organoids could be evaluated, a valuable perspective in the development of personalized therapies. Additionally, important tumour characteristics that regulate the sensitivity of tumour cells to NK cells were identified through CRISPR genetic screens, providing new insights for optimizing NK cell immunotherapy. The research conducted in this thesis contributes to our understanding of the mechanisms behind NK cell activation and inhibition, paving the way for more effective NK cell immunotherapy for cancer treatment.