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Decreased Tumor Surveillance after Adoptive T-Cell Therapy

¹ Tumor Immunology, Department of Clinical Research and ² Institute of Medical Oncology, Inselspital, University of Berne, Berne, Switzerland; ³ Experimental Immunology, University Hospital of Zurich, Zurich, Switzerland; and ⁴ Applied Virology and Gene Therapy, Georg-Speyer-Haus, Frankfurt am Main, Germany

Requests for reprints: Adrian F. Ochsenbein, Institute for Medical Oncology, University of Berne, Freiburgstrasse 10, Inselspital, CH-3010 Bern, Switzerland. Phone: 41-31-632-41-14; Fax: 41-31-382-12-37; E-mail: adrian.ochsenbein{at}insel.ch.

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. [Cancer Res 2007;67(15):7467–76]