Abstract |
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.
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Authors | Diana A Alvarez Arias, Hye-Jung Kim, Penghui Zhou, Tobias A W Holderried, Xuan Wang, Glenn Dranoff, Harvey Cantor |
Journal | Cancer immunology research
(Cancer Immunol Res)
Vol. 2
Issue 3
Pg. 207-16
(Mar 2014)
ISSN: 2326-6074 [Electronic] United States |
PMID | 24778317
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | ©2013 AACR. |
Chemical References |
- Antigens, Neoplasm
- Cancer Vaccines
- Histocompatibility Antigens Class I
- Q surface antigens
- Granulocyte-Macrophage Colony-Stimulating Factor
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Topics |
- Adoptive Transfer
- Animals
- Antigens, Neoplasm
(immunology)
- CD8-Positive T-Lymphocytes
(immunology)
- Cancer Vaccines
(immunology, pharmacology)
- Cell Line, Tumor
- Female
- Granulocyte-Macrophage Colony-Stimulating Factor
(immunology)
- Histocompatibility Antigens Class I
(genetics)
- Melanoma, Experimental
(immunology, therapy)
- Mice
- Mice, Inbred C57BL
- Mutation
- T-Lymphocytes, Cytotoxic
(immunology)
- T-Lymphocytes, Regulatory
(immunology)
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