Surmounting tumor-induced immune suppression by frequent vaccination or immunization in the absence of B cells.
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.
Oizumi
Satoshi
S
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.
Deyev
Vadim
V
Yamazaki
Koichi
K
Schreiber
Taylor
T
Strbo
Natasa
N
Rosenblatt
Joseph
J
Podack
Eckhard R
ER
D019264:Adoptive Transfer; D000818:Animals; D030801:Animals, Genetically Modified; D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D045142:Cross-Priming; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D007117:Immunization, Secondary; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D019139:Tumor Escape
D000970:Antineoplastic Agents; D000939:Epitopes; D007141:Immunoglobulin Fc Fragments; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; C053387:endoplasmin