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Improved vaccine efficacy of tumor exosome compared to tumor lysate loaded dendritic cells in mice

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Leukemia immunotherapy frequently does not meet expectation, one of the handicaps being tumor exosome (TEX)-promoted immunosuppression. We here asked, using the mouse myeloid leukemia WEHI3B and the renal cell carcinoma line RENCA, whether dendritic cell (DC) vaccination suffices to counterregulate...

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Bibliographic Details
Main Authors: Gu, Xiaoyu (Author) , Erb, Ulrike (Author) , Büchler, Markus W. (Author) , Zöller, Margot (Author)
Format: Article (Journal)
Language:English
Published: 2015
In: International journal of cancer
Year: 2014, Volume: 136, Issue: 4, Pages: E74-E84
ISSN:1097-0215
DOI:10.1002/ijc.29100
Online Access:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1002/ijc.29100
Verlag, kostenfrei, Volltext: http://onlinelibrary.wiley.com/doi/10.1002/ijc.29100/abstract
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Author Notes:Xiaoyu Gu, Ulrike Erb, Markus W. Büchler and Margot Zöller
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Summary:Leukemia immunotherapy frequently does not meet expectation, one of the handicaps being tumor exosome (TEX)-promoted immunosuppression. We here asked, using the mouse myeloid leukemia WEHI3B and the renal cell carcinoma line RENCA, whether dendritic cell (DC) vaccination suffices to counterregulate TEX-induced immunosuppression and whether TEX could serve as tumor antigen for DC-loading. DC-vaccination significantly prolonged the survival time of WEHI3B-bearing mice, TEX-loaded DC (DC-TEX) being superior to lysate-loaded DC (DC-lys), even an excess of TEX not interfering with immune response induction. The superior response to DC-TEX was accompanied by an increase in WEHI3B-specific CD4+ T cells, evaluated by trogocytosis and proliferation. Similar findings accounted for DC loaded with RENCA TEX. TEX was efficiently taken-up by DC and TEX uptake supported CD11c, MHCII and IL12 upregulation in DC. Importantly, TEX was partly recruited into the MHCII-loading compartment such that “TEX” presentation time and recovery in T cells significantly exceeded that of tumor-lysate. Thus, TEX did not drive DC into a suppressive phenotype and were a superior antigen due to higher efficacy of TEX-presentation that is supported by prolonged persistence, preferential processing in the MHCII-loading compartment and pronounced trogocytosis by T helper cells. TEX is present in tumor patients' sera. TEX, recovered and enriched from patients' sera, might well provide an optimized, individual-specific antigen source for DC-loading and vaccination.
Item Description:Published online: 28 Jul 2014
Gesehen am 17.07.2017
Physical Description:Online Resource
ISSN:1097-0215
DOI:10.1002/ijc.29100

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