Review Article

Immunotherapy: New rise in cancer treatment

Amir Hossein Mohammadzadeh

Amir Hossein Mohammadzadeh
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Online First: December 29, 2017 | Cite this Article
Mohammadzadeh, A. 2017. Immunotherapy: New rise in cancer treatment. The Cancer Press 3(4). DOI:10.15562/tcp.62

Cancer immunotherapy is currently the hottest topic in the oncology field, under certain circumstances & depending on the initiating stimulus, cancer cell death can be immunogenic or nonimmunogenic. Immunogenic cell death (ICD) involves changes in the composition of the cell surface. Moreover the release of soluble mediators, occurring in a defined temporal sequence. At the molecular level, the immunogenic characteristics of ICD are mainly mediated by damage-associated molecular patterns (DAMPs), which various intracellular molecules like calreticulin (CRT), heat-shock proteins (HSPs), secreted ATP and high mobility group protein B1(HMGB1), have been shown to be DAMPs exposed/secreted in a stress agent/factor-and cell death-specific manner. These discoveries have motivated further research into discovery of new DAMPs, new pathways for their exposure/secretion, search for new agents capable of inducing immunogenic cell death and urge to solve currently present problems with this paradigm. We anticipate that this emerging amalgamation of DAMPs, immunogenic cell death and anticancer therapeutics may be the key towards squelching cancer-related mortalities, in near future. One promising strategy to induce priming of tumor-specific T cells is dendritic cell (DC)-based immunotherapy.  Therefore, they are the most frequently used cellular adjuvant in clinical trials. Since the publication of the first DC vaccination trial in melanoma patients in 1995, the promise of DC immunotherapy is underlined by numerous clinical trials, frequently showing survival benefit in comparison to non-DC control groups. We review some of the latest developments in the DC vaccination field, with a special emphasis on strategies that are applied to obtain a highly immunogenic tumor cell cargo to load and to activate the DCs. To this end, we discuss the effects of immunogenic treatment modalities and potent inducers of immunogenic cell death on DC biology and their application in DC-based immunotherapy in preclinical as well as clinical settings. We therefore anticipate that the comprehension of the mechanisms governing the immunogenicity of cell death will have a profound impact on the design of anticancer therapies and the failure of the majority of therapeutic cancer vaccines tested to date is a reflection of the fact that the design of most of these vaccines preceded a mature understanding of the interaction between developing tumors and the immune system.

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