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Ziegler, A.* ; Heidenreich, R.* ; Braumüller, H.* ; Wolburg, H.* ; Weidemann, S.* ; Mocikat, R. ; Röcken, M.*

EpCAM, a human tumor-associated antigen promotes Th2 development and tumor immune evasion.

Blood 113, 3494-3502 (2009)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords 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
Journal Blood
Quellenangaben Volume: 113, Issue: 15, Pages: 3494-3502 Article Number: , Supplement: ,
Publisher American Society of Hematology
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Immunology (IMI)