Lattice_grid_med
Powered by LatticeGrid

Search Enter term and hit return. Use '*' for as a wildcard.
Zhang H, Merchant MS, Chua KS, Khanna C, Helman LJ, Telford B, Ward Y, Summers J, Toretsky J, Thomas EK, June CH, Mackall CL
Tumor expression of 4-1BB ligand sustains tumor lytic T cells
Cancer Biol Ther (2003) 2:579-86.
Abstract
Inadequate costimulation by solid tumors is generally believed to induce immune tolerance during primary tumor growth. We looked for tumor-specific immunity vs. tolerance in patients with Ewing's sarcoma. Circulating T cells from patients with progressively growing Ewing's tumors displayed MHC restricted tumor-induced proliferation and robust tumor lysis. Tumor-reactive T cells reside within the memory CD3+CD8+ subset and are CD28-/4-1BB+. Autologous Ewing's tumors expressed 4-1BBL, and tumor-induced T cell proliferation and activation required costimulation by 4-1BBL. Stimulation of PBL with anti-CD3/4-1BBL, but not anti-CD3/anti-CD28 induced tumor lytic effectors. Similarly, in a xenograft model, anti-CD3/4-1BBL expanded T cells controlled primary growth and prevented metastasis of autologous tumors while nonactivated and anti-CD3/anti-CD28 activated CD8+ cells did not. These results question prevailing models of tumor induced tolerance accompanying progressive tumor growth; rather, we show coexistence of progressive tumor growth and anti-tumor immunity, with costimulation provided by the tumor itself. They further demonstrate a potential new therapeutic role for 4-1BBL mediated costimulation in expanding tumor reactive CTLs for use in the adoptive immunotherapy of cancer.
Note
Publication Date: 2003-09-01.
Back
Last updated on Saturday, August 22, 2020