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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
EpCAM, a human tumor-associated antigen promotes Th2 development and tumor immune evasion.
Blood 113, 3494-3502 (2009)
Experimental tumor vaccination and adoptive T-cell therapies show that interferon-gamma (IFN-gamma)-producing CD4(+) T helper cells (Th1) can be highly effective in tumor prevention and therapy. Unexpectedly, first vaccine trials in humans revealed that tumor immune therapy may not only be protective, but, on the contrary, even promote tumor progression. Here, we analyzed T-cell immune responses to the epithelial cell adhesion molecule (EpCAM), one of the most common tumor-associated antigens (TAA) serving as immune target in colon cancer patients. Th-cell priming against EpCAM inevitably resulted in interleukin-4 (IL-4)-dominated Th2 responses, even under most stringent Th1-inducing conditions. These EpCAM-reactive Th2 cells rather promoted growth of EpCAM-expressing tumors. To analyze the role of IL-4 in tumor immune evasion, we generated EpCAM-reactive Th1 cells from IL-4.ko mice. These Th1 cells provided tumor-specific protection and established highly protective Th1 memory responses, even in naive BALB/c mice. Inhibition of tumor growth by Th1 cells resulted in intratumoral expression of cytokines of the IL-12 family and of IFN-gamma. Preventing activation-associated death of Th1 cells further increased intratumoral IFN-gamma expression and improved therapeutic efficacy. Thus, human TAA may promote tumor immune evasion by strongly favoring Th2 development.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
t-cell responses; dendritic cells; ifn-gamma; metastatic melanoma; cross-talk; in-vivo; adoptive immunotherapy; cancer-immunotherapy; leishmania-major; angiogenesis
ISSN (print) / ISBN
0006-4971
e-ISSN
1528-0020
Zeitschrift
Blood
Quellenangaben
Band: 113,
Heft: 15,
Seiten: 3494-3502
Verlag
American Society of Hematology
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Molecular Immunology (IMI)