**5.1 Dendritic cells**

138 Cancer Prevention – From Mechanisms to Translational Benefits

**MAPK MEK**

**AKT GSK**

**HER2 HER2**

**HER2**

**Cell Division**

HER-3 has a more ambiguous role in tumorigenesis compared to the other members of the EGFR family. It is frequently expressed in breast, ovarian and lung cancers [62-64]. The role of HER-4 in relationship to tumor development is also not clear. HER-4 mutations have recently been shown to augment proliferation and cell survival in melanomas. Agents that

The HER-2 protein is a well established target of immunotherapy in breast cancer. The proto-oncogene HER-2 is found on chromosome 17q and encodes a transmembrane tyrosine kinase growth factor receptor. HER-2 over expression occurs in ovarian, pancreatic, gastric, lung and head/neck cancers [65-68]. Twenty to thirty percent of breast cancers have been found to amplify the HER-2 gene or overexpress the HER-2 protein, which portends a poorer prognosis and higher risk of recurrence in patients with both invasive and in situ

HER-2 represents an ideal target for antigen-specific vaccines used to treat breast cancer. Over expression of this protein is immunogenic as it induces a T cell immune response causing HER-2 specific antibodies to be present in the serum of breast cancer patient [70].

target HER-4 may be found to be effective against melanoma and other cancers [60].

**Proliferation**

**Survival**

**PI3K**

**HER4**

**PTEN**

**Bad**

**Ligand**

**HER2**

**HER3**

**Apoptosis**

**Survivin**

**HER1**

Fig. 1. The EGF receptor family.

**4.3 HER-2** 

disease [69].

**MUC1**

**HER1**

**RAF RAS SOS**

**GRB2**

**HER1**

**HER2**

**HER3**

**MUC1**

**HER1**

DC vaccines represent one of a number of strategies for vaccinating patients against tumorassociated antigens. DCs are the most powerful of the APCs and are the primary means by which naïve T cells become immunized to specific antigens. DCs are unique in their ability to activate both the innate and adaptive immune systems. Immature DCs arise from progenitors in the bone marrow and then enter the blood stream and circulate throughout the peripheral tissues where they are exposed to foreign antigens. After capturing antigens, DCs undergo a maturation process that ultimately guides their travel to secondary lymphoid tissues. Once in the regional lymph nodes, the DCs process the captured antigen and then display the antigen as a peptide on their MHC molecules. DCs present the peptides to naïve T cells resulting in T lymphocyte expansion and differentiation.

In addition to T cell stimulation, contact with DCs causes activation of B lymphocytes which leads them to differentiate into plasma cells that subsequently release antibodies targeted against the initial pathogen. After antigen exposure, DCs also release cytokines which can activate the cells of the innate immune system, including eosinophils, macrophages, and NK cells. In this way, DCs are capable of activating both the innate and adaptive immunity and are central to the communication between the two immune systems [36, 78-80].
