Antigen quality determines the efficiency of antitumor immune responses generated in the absence of regulatory T cells

Bergot, A-S., Durgeau, A., Levacher, B., Colombo, B. M., Cohen, J. L. and Klatzmann, D. (2010) Antigen quality determines the efficiency of antitumor immune responses generated in the absence of regulatory T cells. Cancer Gene Therapy, 17 9: 645-654. doi:10.1038/cgt.2010.21


Author Bergot, A-S.
Durgeau, A.
Levacher, B.
Colombo, B. M.
Cohen, J. L.
Klatzmann, D.
Title Antigen quality determines the efficiency of antitumor immune responses generated in the absence of regulatory T cells
Journal name Cancer Gene Therapy   Check publisher's open access policy
ISSN 0929-1903
1476-5500
Publication date 2010-09
Sub-type Article (original research)
DOI 10.1038/cgt.2010.21
Volume 17
Issue 9
Start page 645
End page 654
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Abstract The observation that depletion or inhibition of regulatory T cells (Tregs) unleashes efficient antitumor effector immune responses that can lead to tumor eradication in mice has opened new perspectives for the development of cancer immunotherapy. The quality and overall efficiency of the effector immune responses induced in the absence of Tregs seem to depend on multiple factors that determine the result of a battle involving effector T cells (Teffs), Tregs and tumor cells. In this study, we investigated the quality of tumor-associated antigens (TAAs) as one such factor. We show that the presence of a strong dominant antigen is required for the induction of effector responses capable of tumor eradication in the absence of Tregs. The sole addition of a dominant antigen on tumor cells does not change tumor growth in unmanipulated mice, but improves tumor eradication rate from a few to almost 100% in the absence of Tregs. This eradication can be shown to result from the recruitment and activation of specific Teffs recognizing this antigen. We also show that the presence of such dominant antigens has the side effect of restricting the breadth of the immune response to other TAAs, which could favor the generation of escape mutant by tumor editing. Taken together, our results highlight the potential, and some requirements for cancer immunotherapy based on Treg depletion. They also show that, ultimately, tumor fate depends on multiple factors that should all be taken into consideration for the design of more efficient immunotherapy.
Keyword Tumor immunity
Tolerance
Immunodominance
Immunosurveillance
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
UQ Diamantina Institute Publications
 
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