Tumour immunology
The immunological mechanisms involved in cancer growth are highly complex, including tissue-resident and blood-derived cells. Tumour- infiltrating immune cells play a key role against cancer. However, malignant cells are capable of evading the immune response and establishing a very complex balance in which different immune subtypes may drive tumour progression, metastases and resistance to therapy [27]. Cancer cells make high levels of proteins that can switch off the checkpoint proteins in T cells and the T cells can no longer recognise and kill cancer cells. Drugs or antibodies that block checkpoint proteins (checkpoint inhibitors) would prevent the switching-off action of the cancer cells and the T cells can then find and attack the cancer cells. The checkpoint proteins CTLA-4(cytotoxic T lymphocyte associated protein 4) and PD-1 ( programmed cell death protein 1) are found on T cells, and PD-L1 are on cancer cells. The checkpoint inhibitors are used in immunotherapy of cancers but since they boost all the immune cells, and not the ones that target cancer, the overactive T cells can cause possible side effects such as fatigue, nausea, skin rash, pruritus, anorexia, diarrhoea, and breathlessness and dry cough from inflammation of the lungs. They also cause, liver, kidney and thyroid dysfunction [11, 28, 29]. The human immune system mounts natural endogenous response to highly immunogenic tumour cells through a series of steps, including the presenting of tumour antigens to T cells via antigen-presenting cells (APCs), priming and activation of T cells in the lymph nodes, trafficking and infiltration of T-cells into tumour beds, recognition of cancer cells by T cells, development of antigen-specific effector and memory T cells, and humoral immunity, allowing effector T cells and other endogenous immune cells as well as tumour- effective antibodies to tumour to eliminate cancer cells [30]. Monoclonal antibodies made from hybridoma cells by recombinant DNA technology are routinely used in several fields including infections, and targeted cancer therapy. They may also help turn the immune system against cancer i.e. immunotherapy by marking cancer cells for better recognition and destruction. An example is rituximab , which binds to the CD20 on B cells and some types of cancer cells such as lymphomas, causing the immune system to kill them. Other monoclonal antibodies such as blinatumomab bring T cells close to leukaemia cancer cells by binding to both CD19 protein on the surface of leukaemia cells, and CD3, a protein on the surface of T cells which would facilitate the response and killing of the leukaemia cells by the T cells [31].