Targeting STAT3 in adoptively transferred T cells promotes their in vivo expansion and antitumor effects.

ABSTRACT: Adoptive cell therapy with engineered T cells to improve natural immune response and antitumor functions has shown promise for treating cancer. However, the requirement for extensive ex vivo manipulation of T cells and the immunosuppressive effects of the tumor microenvironment limit this therapeutic modality. In the present study, we investigated the possibility to circumvent these limitations by engineering Stat3 -deficient CD8(+) T cells or by targeting Stat3 in the tumor microenvironment. We show that ablating Stat3in CD8(+) T cells prior to their transfer allows their efficient tumor infiltration and robust proliferation, resulting in increased tumor antigen-specific T-cell activity and tumor growth inhibition. For potential clinical translation, we combined adoptive T-cell therapy wi

SUBMITTER: Kujawski M 

PROVIDER: S-EPMC3017475 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature