IFN-γ-Dependent Inhibition of Tumor Angiogenesis by Tumor-Infiltrating CD4+ T Cells Requires Tumor Responsiveness to IFN-γ

Abstract

The importance of CD4+ T cells in the induction of an optimal antitumor immune response has largely been attributed to their ability to provide costimulatory signals for the priming of MHC class I-restricted CD8+ CTL. However, many reports have demonstrated a requirement for CD4+ T cells in the effector phase of tumor rejection indicating a greater responsibility for CD4+ T cells in controlling tumor outgrowth. We demonstrate here a critical role for CD4+ T cells in restraining initial tumor development through the inhibition of tumor angiogenesis. Using a tumor variant that is unresponsive to IFN-γ, we show that tumor responsiveness to IFN-γ is necessary for IFN-γ-dependent inhibition of tumor angiogenesis by CD4+ T cells. These studies reveal a pivotal role for CD4+ T cells in controlling early tumor development through inhibition of tumor angiogenesis.