Hanne Verswyvel

Chapter 1 │ Page 12 Figure 1: The cancer immunity cycle with potential sites of intervention discussed in this PhD dissertation. Innate NK cell immunity cycle and the traditional concept of the cancer immunity cycle (T cell-based immunity) as partners in crime. NTP and subsequent immunological e ects can stimulate several crucial steps in this process, ultimately resulting in improved ICI e icacy. Various aspect from this cycle are explained in more detail in the following text. Adapted from Bald et al. (2020)[15] and Mellman et al. (2023)[12]. 1.2. The Strengths and Weaknesses of Immunotherapy Immunotherapy has revolutionized the landscape of cancer treatment by leveraging the patient’s own immunity to eradicate malignancies. Various types of immunotherapy exist, like immune checkpoint inhibitors (ICI)[16-18], adoptive cell transfers (e.g. CAR-T or CAR-NK cell therapies) [19, 20], and cancer vaccines [21]. Among these, ICI targeting Programmed Death (Ligand) 1 (PD-1/PD-L1) and Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA-4) represent a major breakthrough in cancer therapy, highlighted by unparalleled treatment e icacy and durability, and survival benefits across multiple cancers [16, 18]. As a result, they have been established as a first-line treatment in various cases and disease stages [22, 23]. Three main classes of ICIs have received approval from the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) for the treatment of

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