15353-j-veluchamy

8 | Chapter 1 General introduction Cancer comprises a class of diseases characterized by uncontrolled cell growth and invasion. Well known external factors contributing to cancer in humans are mainly related to unhealthy diet patterns, tobacco use, heavy consumption of alcohol, and prolonged exposure to carcinogenic chemicals and ionizing radiations 1 . Further, hereditary defects in the genetic make-up, viral infections and chronic inflammation can also predispose to cancer. Although advances in cancer research have contributed to better survival over recent years, certain challenges remain to be addressed 2,3 . Tumors are broadly classified into hematological (cancers of the blood) and solid tumors (affects tissues/organs). Tumors can either be benign (not cancer), or malignant (cancer) 4 . Upon diagnosis, malignant solid tumors are treated by conventional methods (surgery, chemotherapy and radiotherapy) to reduce the tumor mass. However, once metastatic disease has developed these cancers are generally not curable. Therefore, concerted research is required to develop novel treatments that will improve patients’ outcome. Our immune system is a collection of immune effector subsets and molecules employed by our body to fight several diseases, including cancer. In a healthy individual, cells of the immune system such as B cells, T cells, and Natural Killer (NK) cells are thymus and/or bone marrow derived and distributed throughout the body providing specific and non-specific protection against viruses, bacteria and cancer cells 5 . B cells differentiate into plasma cells and produce antibodies that can direct immunity to specific targets (i.e. adaptive humoral immunity). T cells are the principal effectors responsible for cell mediated adaptive immunity and require antigen presentation by professional antigen presenting cells such as macrophages and dendritic cells. NK cells are part of the innate immune defense. They can identify stressed cells and provide a first line of protection against various infections but also against cancer cells 6, 7 . Natural killer cells in oncology So far T cells have been the mainstay of cancer immunotherapy approaches that focus on adoptive cell therapy. It is generally recognized that NK cells play an essential role in anti- tumor immunity. Certainly, in case of the prevention of metastases through the elimination of circulating cancer stem cells with a high metastatic potential, NK cells are recognized to be the main immune effector cells 8 . Moreover, as solid tumors have a propensity to down-regulate MHC-I, NK cells provide a failsafe mechanism in these circumstances where cytotoxic T cells, which depend on MHC-I for tumor recognition and elimination, are debilitated. NK cells have recently been more intensely explored as a viable therapeutic platform next to T cell-based approaches.