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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Animals, Genetically Modified
  • Antineoplastic Agents / immunology
  • Antineoplastic Agents / therapeutic use
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cross-Priming
  • Cytotoxicity, Immunologic
  • Epitopes
  • Immunization, Secondary*
  • Immunoglobulin Fc Fragments / genetics
  • Immunoglobulin Fc Fragments / immunology
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • Neoplasms, Experimental / immunology
  • Neoplasms, Experimental / therapy*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / therapeutic use
  • Tumor Escape*


  • Antineoplastic Agents
  • Epitopes
  • Immunoglobulin Fc Fragments
  • Membrane Glycoproteins
  • Recombinant Fusion Proteins
  • endoplasmin