Tumor growth is associated with inhibition of host anti-tumor 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 MHC class Ib molecule Qa-1 that impairs CD8 Treg suppressive activity. Here, we report that growth of B16 melanoma is substantially delayed in these Qa-1 mutant mice after therapeutic immunization with B16 melanoma cells engineered to express GM-CSF compared to Qa-1 B6.WT controls. Reduced tumor growth is associated with enhanced expansion of follicular T helper cells, germinal center B cells, high titers of anti-tumor autoantibodies, which provoke robust anti-tumor 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 Treg cells. 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 Treg represents a potentially effective strategy to enhance anti-tumor immunity.
- Received August 13, 2013.
- Revision received November 12, 2013.
- Accepted December 9, 2013.
- Copyright © 2013, American Association for Cancer Research.