Immunotherapy system can be manipulated to target and eliminate

constitutes one of the latest approaches to fight cancer, based on the concept
that the immune system can be manipulated to target and eliminate malignant
cells. The idea that tumors can be recognized by the immune system dates back
to 1893, when William Coley used bacteria to treat different types of cancers
by activating
the immune system1. However, inadequate understanding of these
mechanisms, led to the use of surgery and radiotherapy being the only established therapies
in 20th century2. Afterwards, Thomas and Burnet introduced the
theory of immune surveillance, which refers to the ability of the immune system
to continuously detect cancer cells appeared in the body and eliminate them3,4

It is known now that immune
surveillance is necessary for inhibiting cancer onset. Various genetic and
epigenetic changes taking place in tumors provide them with neoantigens, which are
recognized 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. More
specifically, tumor cells are imposed to a selection pressure by the
attacking immune system, which eliminates the more vulnerable ones, leading to
the survival of the less immunogenic cells that have also acquired resistance to
the immune response. This is known as the equilibrium phase, a long lasting
process that usually results in the emergence of an occult disease. When the
immune system is no longer able to maintain this balance, immune escape takes
place and constant tumor growth occurs leading to possible malignancies4.
(Figure 1)

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GC Prendergast, Oncogene 2008

Figure 1: Phases of
immunoediting during tumor progression.



After decades of conflicting
clinical results, immunotherapy has now entered a new era, as it is considered
to be a highly promising therapeutic tool against cancer. A large number of
encouraging new clinical trials have contributed to the establishment of immunotherapy
as a safe and acceptable treatment6. Several immunotherapeutic methods
have been developed including monoclonal antibodies, adoptive cell therapy and
cancer vaccines. More specifically, antibodies against cytotoxic T-lymphocyte- associated
protein 4 (CTLA-4) and programmed cell death 1 (PD-1), known as checkpoint
inhibitors 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 the
antitumor properties of T-cells by increasing the amount of attacking
lymphocytes ex vivo and transferring them back into the patient, for
eliminating cancer cells 8,9. As for the use of vaccines, they are
based on the activation of dendritic cells, and subsequently tumor specific
T-cells which can attack the tumor directly. However, numerous limitations have
led to the development of only one vaccine approved by the U.S. Food and Drug
Administration (FDA) until now10.



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