Innate immune response to tumour cells
Cancer cells can alter the steady state activity of all myeloid cells present in the tumour microenvironment by secreting IL-6 or granulocyte-macrophage colony-stimulating factor ( GM-CSF), that induce the recruitment of immature myeloid cells to tumour cells, as well as cell proliferation. Natural killer cells (NKL) can kill target cells without the need for prior activation. As many neoplastic cells lose the expression of MHC-I during malignant transformation which at normal levels inhibit NK cells, they continue to express ligands (e.g. glycolipid) that activate NK cells. This recognition mechanism further leads to the progression of anti- tumour immune response through the production of interferon-λ which activate a number of interferon- λ signalling pathways that enhances the killing of a proportion of the tumour, induces the production of chemokines that further recruits more cells in the innate immune system, activates macrophages that express tumoricidal products (reactive oxygen and nitrogen metabolites) and, tumour necrosis factor(TNF) that activates endothelial cells and coagulation leading to tumour necrosis, and directly stimulates apoptosis. Moreover, the cytokines, IL-12. IL-15, and the type 1 interferons stimulate NK cells, which leads to proliferation and increased cytotoxic activity [32].