Pancreatic cancer: Role of the immune system in cancer progression and vaccine-based immunotherapy

Figures & data

Figure 1. Diagrammatic representation of most immune treatment strategies under investigation in pancreatic cancer.

Figure 2. Tumor immune microenvironment and cancer progression.

Table 1. Most significant antigens associated with pancreatic cancer

Antigen	Location	Tumor expression	Characteristics/Functions	Significative Reference
CEA	Cell surface (GPI-linked)	Over-expressed	Glycoprotein, normally expressed only in oncofetal tissues. Functions as cell-adhesion molecule. First tumor antigen to be described.	E. H. Huang et al. CEA-based vaccines. Expert Review of Vaccines vol. One, no.1, pp. 49–63, 2002.
Her2-neu	Transmembrane	Overexpressed	A receptor tyrosine kinase, member of the EGF-receptor family, involved in cell growth and differentiation.	S. Lei, et al. Overexpression of HER2/neu oncogene in pancreatic cancer correlates with shortened survival. International Journal of Pancreatology, vol. Seventeen, no. One, pp. Fifteen–21, 1995.
MUC-1	Transmembrane	Over-expressed, hypo-glycosylation	Type I transmembrane glycoprotein, expressed on apical surface of ductal and glandular epithelial cells at low levels. Extracellular domain has a polypeptide core with multiple tandem repeats of 20 aminoacids.	C. K. Tang et al. Strategies used for MUC1 immunotherapy: human clinical studies, Expert Review of Vaccines, vol. Seven, no. Seven, pp. 963–975, 2008.
P53	Intracellular	Mutated self	Tumor suppressor that regulates cell cycle. Normally inhibits surviving at the transcription level and can initiate apoptosis if DNA damage is irreparable.	F. Chen et al. Current strategies to target p53 in cancer, Biochemical Pharmacology, vol. 80, no. Five, pp. 724–730, 2010.
Survivin	Intracellular	Overexpressed	Member of IAP family. Inhibits caspase activation; is found in most human tumors and fetal tissue, but is completely absent in terminally differentiated cells.	B. M. Ryan et al. Survivin: a new target for anti-cancer therapy, Cancer Treatment Review, vol. 35, no. Seven, pp. 553–562, 2009.
K-Ras	Intracellular	Mutated self	Mutated form of ras, a GTPase important for cell proliferation, differentiation and survival.	C. Almoguera et al. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes, Cell, vol. 53, no. Four, pp. 549–554, 1988.
Telomerase	Intracellular	Over-expressed	Ribonucleoprotein that is responsible for RNA dependent synthesis of telomeric DNA. TERT is its catalytic subunit.	E. Hiyama et al. Telomerase activity is detected in pancreatic cancer but not in benign tumors, Cancer Research, vol. 57, no. Two, pp. 326–331, 1997.
VEGFR2	Transmembrane	Overexpressed	A tyrosine kinase and member of platelet derived growth factor family. Receptor for VEGF with functions in blood vessel development.	J. Itakura et al. Enhanced expression of vascular endothelial growth factor in human pancreatic cancer correlates with local disease progression. Clinical Cancer Research, vol. Three, no. Eight, pp. 1309–1316, 1997.
Mesothelin	Cell surface (GPI-linked)	Over-expressed	GPI-linked glycoprotein, expressed on the surface of mesothelial cells lining the pleura, peritoneum and pericardium at low levels. Binding partner of CA125/MUC16.	M. Li, et al. Mesothelin is a malignant factor and therapeutic vaccine target for pancreatic cancer, Molecular Cancer Therapeutics, vol. Seven, no. Two, pp. 286–296, 2008.
Alfa-enolase	Cell surface, Intracellular	Overexpressed, post-translational modified (i.e., acetylated)	Glycolytic enzyme that also acts as a surface plasminogen receptor. Is found in a variety of tissue, on the cell surface as well as within the nucleus and cytosol.	W. Zhou et al. Mass spectrometry analysis of the post-translational modifications of α-enolase from pancreatic ductal adenocarcinoma cells, Journal of Proteome Reasearch, vol. Nine, no. Six, pp. 2929–36, 2010.