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

Satoshi Oizumi, Vadim Deyev, Koichi Yamazaki, Taylor Schreiber, Natasa Strbo, Joseph Rosenblatt, Eckhard R. Podack

Research output: Contribution to journalArticle

34 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)394-401
Number of pages8
JournalJournal of Immunotherapy
Volume31
Issue number4
DOIs
StatePublished - May 1 2008

Keywords

  • B-cell de.ciency/depletion
  • Frequent vaccination
  • Secreted HSP gp96 vaccine
  • Tumor-induced immunosuppression

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

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