Enhancement of Antitumor Immunity by CTLA-4 Blockade

TLDR

Tumor immunogenicity is limited partly because they lack CD28 costimulatory signals, and CTLA‑4 functions as a negative regulator of T cell activation. In vivo blockade of CTLA‑4 with antibodies caused rejection of established tumors and conferred immunity to secondary tumor challenge, demonstrating that inhibiting CTLA‑4 can potentiate effective anti‑tumor immune responses.

Abstract

One reason for the poor immunogenicity of many tumors may be that they cannot provide signals for CD28-mediated costimulation necessary to fully activate T cells. It has recently become apparent that CTLA-4, a second counterreceptor for the B7 family of costimulatory molecules, is a negative regulator of T cell activation. Here, in vivo administration of antibodies to CTLA-4 resulted in the rejection of tumors, including preestablished tumors. Furthermore, this rejection resulted in immunity to a secondary exposure to tumor cells. These results suggest that blockade of the inhibitory effects of CTLA-4 can allow for, and potentiate, effective immune responses against tumor cells.