Tumor surveillance and immune evasion: the interplay between the immune system and tumor cells

Abstract

This thesis encloses the interplay between the immune system and tumor cells. The immune system is, next to defending the body against pathogens, specialized in tumor cell recognition and elimination in various ways. NK-cells, NKT-cells, CD8+ T-cells, and γδ T-cells are important players in tumor surveillance. Tumor cells are distinguished from healthy cells by the expression of tumor-specific antigens (TSA) and tumor-associated antigens (TAA). Diverse receptors on the before mentioned immune cells recognize these antigens, leading to immune cell activation and it provides a license to kill. The main killing mechanisms are the perforin / granzyme pathway, the death-receptor pathways, and antibody-dependent cell-mediated cytotoxicity (ADCC). Attacking tumor cells is accompanied by the production of cytokines, primarily interferon gamma (IFN-γ). IFN-γ steers into an anti-tumor, Th1 direction. Tumor surveillance is counteracted by immune evasion performed by tumor cells and cells in tumor microenvironment (TME), like myeloid-derived suppressor cells (MDSC). Tumor cells (and associated cells) developed many possibilities to evade the immune system; they prevent recognition by immune cells, become apoptosis resistant, deceive the immune system, inhibit immune cell development, proliferation, and maturation or induce immune tolerance. MDSCs are important players in tumor immune evasion and are discussed more thoroughly.