1. Primary Antitumor Immune Response Mediated by CD4+ T Cells
- Author
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Corthay, Alexandre, Skovseth, Dag K., Lundin, Katrin U., Røsjø, Egil, Omholt, Hilde, Hofgaard, Peter O., Haraldsen, Guttorm, and Bogen, Bjarne
- Subjects
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LYMPHOCYTES , *CANCER , *T cells , *MYELOMA proteins - Abstract
Summary: Gene-targeted mice have recently revealed a role for lymphocytes and interferon-γ (IFNγ) in conferring protection against cancer, but the mechanisms remain unclear. Here, we have characterized a successful primary antitumor immune response initiated by naive CD4+ T cells. Major histocompatibility complex class II (MHC-II)-negative myeloma cells injected subcutaneously into syngeneic mice were surrounded within 3 days by macrophages that captured tumor antigens. Within 6 days, naive myeloma-specific CD4+ T cells became activated in draining lymph nodes and subsequently migrated to the incipient tumor site. Upon recognition of tumor-derived antigenic peptides presented on MHC-II by macrophages, the myeloma-specific CD4+ T cells were reactivated and started to secrete cytokines. T cell-derived IFNγ activated macrophages in close proximity to the tumor cells. Tumor cell growth was completely inhibited by such locally activated macrophages. These data indicate a mechanism for immunosurveillance of MHC-II-negative cancer cells by tumor-specific CD4+ T cells through collaboration with macrophages. [Copyright &y& Elsevier]
- Published
- 2005
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