Hanne Verswyvel

Chapter 1 │ Page 11 1. GENERAL INTRODUCTION 1.1. The Persistent Challenge of Cancer Management and the Importance of Anti-Cancer Immunity Cancer remains one of the leading causes of death worldwide, with high mortality and quality-of-life impact, due to its aggressive nature, therapy resistance and immune evasion mechanisms[1-3]. Despite advancements in conventional therapies, including surgery, chemotherapy and radiation, many cancer cases remain incurable, especially in the advanced stages of the disease [4-6]. Cancerous growth is a highly persistent and dynamic process with complex interactions between tumor cells, immune cells and stromal components[7]. The tumor microenvironment (TME) is therefore a key determinant in disease progression and treatment outcome[8], and it is the consensus now that successful cancer treatment can not solely rely on direct tumor eradication but must also harness and restore anti-tumor immunity and disarm the TME [9, 10]. The immune system plays a critical role as the first-line defense mechanism, naturally capable of identifying and eliminating abnormal cells through immune surveillance and e ective intervention [11]. This intricate interaction is best captured in the cancer immunity cycle (Figure 1), a multi-step process in which tumor antigens must be released from dying cancer cells, presented by antigenpresenting cells (APCs), and recognized by cytotoxic T lymphocytes (CTLs) to stimulate an e ective immune response [12]. However, tumors can develop immune-evading mechanisms that suppress key aspects of this process, including damping antigen presentation, or abolish immune cell infiltration and cytotoxic activity[13, 14]. Restoring and enhancing anti-tumor immunity has thus become a major focus in oncology, leading to revolutionary breakthroughs in immunotherapy.

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