Immunotherapy treat different types of cancers by

Immunotherapyconstitutes one of the latest approaches to fight cancer, based on the conceptthat the immune system can be manipulated to target and eliminate malignantcells. The idea that tumors can be recognized by the immune system dates backto 1893, when William Coley used bacteria to treat different types of cancersby activatingthe immune system1. However, inadequate understanding of thesemechanisms, led to the use of surgery and radiotherapy being the only established therapiesin 20th century2. Afterwards, Thomas and Burnet introduced thetheory of immune surveillance, which refers to the ability of the immune systemto continuously detect cancer cells appeared in the body and eliminate them3,4.It is known now that immunesurveillance is necessary for inhibiting cancer onset. Various genetic andepigenetic changes taking place in tumors provide them with neoantigens, which arerecognized as foreign by the immune system of the host in order to be destroyed5.

However,cancer cells are able to escape from the attack of the immune system. Morespecifically, tumor cells are imposed to a selection pressure by theattacking immune system, which eliminates the more vulnerable ones, leading tothe survival of the less immunogenic cells that have also acquired resistance tothe immune response. This is known as the equilibrium phase, a long lastingprocess that usually results in the emergence of an occult disease. When theimmune system is no longer able to maintain this balance, immune escape takesplace and constant tumor growth occurs leading to possible malignancies4.(Figure 1)                                                             GC Prendergast, Oncogene 2008 Figure 1: Phases ofimmunoediting during tumor progression.  After decades of conflictingclinical results, immunotherapy has now entered a new era, as it is consideredto be a highly promising therapeutic tool against cancer.

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A large number ofencouraging new clinical trials have contributed to the establishment of immunotherapyas a safe and acceptable treatment6. Several immunotherapeutic methodshave been developed including monoclonal antibodies, adoptive cell therapy andcancer vaccines. More specifically, antibodies against cytotoxic T-lymphocyte- associatedprotein 4 (CTLA-4) and programmed cell death 1 (PD-1), known as checkpointinhibitors because they normally inhibit the T- lymphocyte prolonged activation,have been identified as successful therapies for subsets of cancer patients7.Adoptive cell therapy constitutes an individualized method, which exploits theantitumor properties of T-cells by increasing the amount of attackinglymphocytes ex vivo and transferring them back into the patient, foreliminating cancer cells 8,9. As for the use of vaccines, they arebased on the activation of dendritic cells, and subsequently tumor specificT-cells which can attack the tumor directly.

However, numerous limitations haveled to the development of only one vaccine approved by the U.S. Food and DrugAdministration (FDA) until now10.                                                                                                                                

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