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J Immunother. 2008 May;31(4):394-401. doi: 10.1097/CJI.0b013e31816bc74d.

Surmounting tumor-induced immune suppression by frequent vaccination or immunization in the absence of B cells.

Author information

1
Department of Microbiology and Immunology, Division of Hematology and Oncology and Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, Miami, FL 33136, USA.

Abstract

Tumor-induced immune suppression is one of the most difficult obstacles to the success of tumor immunotherapy. Here, we show that established tumors suppress CD8 T cell clonal expansion in vivo, which is normally observed in tumor-free mice upon antigen-specific glycoprotein (gp) 96-chaperone vaccination. Suppression of CD8 T-cell expansion by established tumors is independent of tumor-associated expression of the antigen that is recognized by the CD8-T-cell receptor. Vaccination of tumor-bearing mice is associated with increased cellular recruitment to the vaccine site compared with tumor-free mice. However, rejection of established, suppressive tumors required frequent (daily) gp96 vaccination. B cells are known to attenuate T helper cell-1 responses. We found that in B-cell deficient mice, tumor rejection of established tumors can be achieved by a single vaccination. Accordingly, in tumor-free B-cell deficient mice, cognate CD8 cytotoxic T lymphocyte clonal expansion is enhanced in response to gp96-chaperone vaccination. The data have implications for the study of tumor-induced immune suppression and for translation of tumor immunotherapy into the clinical setting. Frequent vaccination with cellular vaccines and concurrent B-cell depletion may greatly enhance the activity of anticancer vaccine therapy in patients.

PMID:
18391756
DOI:
10.1097/CJI.0b013e31816bc74d
[Indexed for MEDLINE]

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