Decreased tumor surveillance after adoptive T-cell therapy.
The effect of cancer immunotherapy on the endogenous immune response against tumors is largely unknown. Therefore, we studied immune responses against murine tumors expressing the glycoprotein (GP) and/or nucleoprotein of lymphocytic choriomeningitis virus (LCMV) with or without adoptive T-cell therapy. In nontreated animals, CTLs specific for different epitopes as well as LCMV-GP-specific antibodies contributed to tumor surveillance. Adoptive immunotherapy with monoclonal CTLs specific for LCMV-gp33 impaired the endogenous tumor-specific antibody and CTL response by targeting antigen cross-presenting cells. As a consequence and in contrast to expectations, immunotherapy enhanced tumor growth. Thus, for certain immunogenic tumors, a reduction of tumor-specific B- and T-cell responses and enhanced tumor growth may be an unwanted consequence of adoptive immunotherapy.
Tumor Immunology, Department of Clinical Research, Inselspital, University of Berne, Berne, Switzerland.
Matthias
M
Matter
Viktor
V
Pavelic
Daniel D
DD
Pinschewer
Sabine
S
Mumprecht
Bruno
B
Eschli
Tsanan
T
Giroglou
Dorothee
D
von Laer
Adrian F
AF
Ochsenbein
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D002857:Chromium / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005354:Fibrosarcoma / Q000276:immunology / Q000628:therapy*; D005434:Flow Cytometry; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009698:Nucleoproteins / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology / Q000378:metabolism
D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D018398:Homeodomain Proteins; D009698:Nucleoproteins; D010446:Peptide Fragments; D014764:Viral Proteins; C094246:nucleoprotein peptide 118-126, lymphocytic choriomeningitis virus; D002857:Chromium; C064658:RAG-1 protein; D007371:Interferon-gamma