Selective Activation of Intracellular Signalling Pathways in Dendritic Cells for Cancer Immunotherapy

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)

Volume 16, 12 Issues, 2016

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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex

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Selective Activation of Intracellular Signalling Pathways in Dendritic Cells for Cancer Immunotherapy

Anti-Cancer Agents in Medicinal Chemistry, 12(1): 29-39.

Author(s): Frederick Arce, Grazyna Kochan, Karine Breckpot, Holly Stephenson and David Escors.

Affiliation: Windeyer Institute of Medical Sciences. 46 Cleveland Street. WT1 4JF London. United Kingdom.


One of the major challenges in achieving effective anti-cancer immunotherapy is to counteract immunological tolerance. Most tumor-associated antigens (TAAs) are sensed as self. Hence, naturally occurring tolerance towards them has to be overcome. Fortunately, there is increasing evidence that anti-tumor immune responses occur and play a crucial role in the success of well-established anti-neoplastic therapies such as radiotherapy and chemotherapy. In fact, their effectiveness relies on signalling by pattern recognition receptors such as Toll-like receptors (TLRs). TLR signal transduction involves activation of a few well-known pathways, of which nuclear factor κB (NF-κB) and mitogen activated protein kinases (MAPKs) are possibly the best characterized. Therefore, constitutive activation of these pathways in immune cells can potentially enhance anti-tumor immunity, especially when targeted to professional antigen presenting cells (APCs) such as dendritic cells (DCs). Several strategies have been devised to test this hypothesis, including constitutive activation of TLRs, NF-κB and MAPKs (extracellular-signal regulated kinase (ERK), p38 and c-Jun kinase 1 (JNK1)). Activation of these pathways in mouse and human DCs has differential effects in immunogenicity and in many cases, enhanced antitumor immunity in pre-clinical models, establishing the basis for future clinical applications.


Cancer, Cytokine, Dendritic cells, Immunotherapy, Lentivector, Signalling, Tolerance, TLR, Tumor, Biosafety.

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Article Details

Volume: 12
Issue Number: 1
First Page: 29
Last Page: 39
Page Count: 11
DOI: 10.2174/187152012798764679

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