[HTML][HTML] Primary antitumor immune response mediated by CD4+ T cells

A Corthay, DK Skovseth, KU Lundin, E Røsjø, H Omholt… - Immunity, 2005 - cell.com
A Corthay, DK Skovseth, KU Lundin, E Røsjø, H Omholt, PO Hofgaard, G Haraldsen
Immunity, 2005cell.com
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 …
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.
cell.com