Disruption of CD8+ Treg activity results in expansion of T follicular helper cells and enhanced antitumor immunity.
| Autor: | Alvarez Arias DA; Authors' Affiliations: Departments of Department of Gastroenterology, Hepatology, and Infectious Diseases, University of Düsseldorf, Düsseldorf, Germany., Kim HJ, Zhou P, Holderried TA, Wang X, Dranoff G, Cantor H |
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| Jazyk: | angličtina |
| Zdroj: | Cancer immunology research [Cancer Immunol Res] 2014 Mar; Vol. 2 (3), pp. 207-16. Date of Electronic Publication: 2013 Dec 31. |
| DOI: | 10.1158/2326-6066.CIR-13-0121 |
| Abstrakt: | Tumor growth is associated with the inhibition of host antitumor immune responses that can impose serious obstacles to cancer immunotherapy. To define the potential contribution of Qa-1-restricted CD8 regulatory T cells (Treg) to the development of tumor immunity, we studied B6.Qa-1 D227K mice that harbor a point mutation in the MHC class Ib molecule Qa-1 that impairs CD8 Treg suppressive activity. Here, we report that the growth of B16 melanoma is substantially delayed in these Qa-1-mutant mice after therapeutic immunization with B16 melanoma cells engineered to express granulocyte macrophage colony-stimulating factor compared with Qa-1 B6-WT controls. Reduced tumor growth is associated with enhanced expansion of follicular T helper cells, germinal center B cells, and high titers of antitumor autoantibodies, which provoke robust antitumor immune responses in concert with tumor-specific cytolytic T cells. Analysis of tumor-infiltrating T cells revealed that the Qa-1 DK mutation was associated with an increase in the ratio of CD8(+) T effectors compared with CD8 Tregs. These data suggest that the CD8(+) T effector-Treg ratio may provide a useful prognostic index for cancer development and raise the possibility that depletion or inactivation of CD8 Tregs represents a potentially effective strategy to enhance antitumor immunity. (©2013 AACR.) |
| Databáze: | MEDLINE |
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