SA-4-1BBL costimulation inhibits conversion of conventional CD4+ T cells into CD4+ FoxP3+ T regulatory cells by production of IFN-γ.

ABSTRACT: Tumors convert conventional CD4(+) T cells into induced CD4(+)CD25(+)FoxP3(+) T regulatory (iTreg) cells that serve as an effective means of immune evasion. Therefore, the blockade of conventional CD4(+) T cell conversion into iTreg cells represents an attractive target for improving the efficacy of various immunotherapeutic approaches. Using a novel form of 4-1BBL molecule, SA-4-1BBL, we previously demonstrated that costimulation via 4-1BB receptor renders both CD4(+)and CD8(+) T effector (Teff) cells refractory to inhibition by Treg cells and increased intratumoral Teff/Treg cell ratio that correlated with therapeutic efficacy in various preclinical tumor models. Building on these studies, we herein show for the first time, to our knowledge, that signaling through 4-1BB inhibits antigen-

SUBMITTER: Madireddi S 

PROVIDER: S-EPMC3411638 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature