A Trojan1, R Giger, N Rist, R F Speck. 1. Dept. of Oncology, University Hospital of Zurich, Raemistr. loo100, CH- 8og91 Zurich, Switzerland. andreas.trojan@usz.ch
Abstract
BACKGROUND: Patients with hematological malignancies are at increased risk for various infections. In patients with solid cancer, a variety of immunosuppressive mechanisms affecting T-cell response are described. We hypothesized that patients with advanced solid tumors may exhibit an impaired recognition of viral antigens. To test this, the capability of CD8+ T cells to recognize recall antigens from influenza and vaccinia virus was compared in patients and healthy individuals. Since all patients and most of the healthy individuals had been vaccinated against vaccinia years ago, comparison of the two groups was expected to be especially informative with respect to distinct effector T-cell reactivity. MATERIALS AND METHODS: Our test population included 16 healthy individuals and 12 patients with advanced solid cancers who were currently not receiving chemotherapy. We stimulated peripheral blood mononuclear cells (PBMC) ex vivo with the well-characterized influenza A matrix 58-66 peptide and the immunogenic and HLA-A*0201 restricted peptide epitope SLSAYIIRV derived from the modified vaccinia virus Ankara (MVA). A specific CD8+ T-cell reactivity was determined by quantitative real-time polymerase chain reaction (qRT-PCR) measuring changes in interferon gamma (IFN-gamma) mRNA expression levels. RESULTS: We found that significantly fewer cancer patients than healthy individuals exhibited specific T-cell recognition of the vaccinia epitope (25% and 69%, respectively). In addition, strength of the T-cell responses against both viral peptides was significantly reduced in cancer patients. CONCLUSION: Patients with advanced tumors are Less likely to mount a T-cell response against viral epitopes. These findings may have implications for the design of immunotherapeutic interventions against virus-induced diseases, including tumors.
BACKGROUND:Patients with hematological malignancies are at increased risk for various infections. In patients with solid cancer, a variety of immunosuppressive mechanisms affecting T-cell response are described. We hypothesized that patients with advanced solid tumors may exhibit an impaired recognition of viral antigens. To test this, the capability of CD8+ T cells to recognize recall antigens from influenza and vaccinia virus was compared in patients and healthy individuals. Since all patients and most of the healthy individuals had been vaccinated against vaccinia years ago, comparison of the two groups was expected to be especially informative with respect to distinct effector T-cell reactivity. MATERIALS AND METHODS: Our test population included 16 healthy individuals and 12 patients with advanced solid cancers who were currently not receiving chemotherapy. We stimulated peripheral blood mononuclear cells (PBMC) ex vivo with the well-characterized influenza A matrix 58-66 peptide and the immunogenic and HLA-A*0201 restricted peptide epitope SLSAYIIRV derived from the modified vaccinia virus Ankara (MVA). A specific CD8+ T-cell reactivity was determined by quantitative real-time polymerase chain reaction (qRT-PCR) measuring changes in interferon gamma (IFN-gamma) mRNA expression levels. RESULTS: We found that significantly fewer cancerpatients than healthy individuals exhibited specific T-cell recognition of the vaccinia epitope (25% and 69%, respectively). In addition, strength of the T-cell responses against both viral peptides was significantly reduced in cancerpatients. CONCLUSION:Patients with advanced tumors are Less likely to mount a T-cell response against viral epitopes. These findings may have implications for the design of immunotherapeutic interventions against virus-induced diseases, including tumors.