Improved vaccine efficacy of tumor exosome compared to tumor lysate loaded dendritic cells in mice
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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| Hauptverfasser: | , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2015
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| In: |
International journal of cancer
Year: 2014, Jahrgang: 136, Heft: 4, Pages: E74-E84 |
| ISSN: | 1097-0215 |
| DOI: | 10.1002/ijc.29100 |
| Online-Zugang: | 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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| Verfasserangaben: | Xiaoyu Gu, Ulrike Erb, Markus W. Büchler and Margot Zöller |
MARC
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| 245 | 1 | 0 | |a Improved vaccine efficacy of tumor exosome compared to tumor lysate loaded dendritic cells in mice |c Xiaoyu Gu, Ulrike Erb, Markus W. Büchler and Margot Zöller |
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| 520 | |a 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. | ||
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